P De Martino

Lack of association between the 3092 T→C Clock gene polymorphism and cluster headache

Recent studies suggested that genetic factors play a role in cluster headache (CH). However, the type and the number of genes involved in the disease are still unclear. We performed an association study in a cohort of Italian CH patients to evaluate whether a particular allele or genotype of the Clock gene would modify the occurrence and the clinical features of the disease. One hundred and seven CH patients, diagnosed according to the International Classification of Headache Disorders, 2nd Edition, (ICHD-II) criteria, and 210 healthy age, sex and ethnicity-matched controls were genotyped for the 3092 T°C Clock gene polymorphism (also known as 3111 T°C). Phenotype and allele frequencies were similarly distributed in CH patients and controls. The clinical features of the disease were not significantly influenced by different genotypes. In conclusion, our study suggests that the 3092 T°C polymorphism of the Clock gene is unlikely to play an important role in cluster headache.

Association between migraine and HLA–DRB1 gene polymorphisms

We examined the distribution of HLA–DRB1 alleles in a cohort of 255 Italian migraine patients and in a control group of 325 healthy subjects. The frequency of DRB1*12 allele was found to be significantly reduced (p=0.02) in patients with migraine while the DRB1*16 allele was significantly increased (p=0.04) in comparison with controls. When the patients were divided into disease subgroups (migraine with and without aura), HLA–DRB1**16 allele was significantly increased (p<0.05) only in migraine without aura patients. We conclude that, in Italian patients, migraine is associated with different alleles of the HLA–DRB1 locus. Our data suggest the presence of a genetic susceptibility factor for migraine within the HLA region.

Headache attributed to spontaneous low CSF pressure: report of three cases responsive to corticosteroids.

The therapy of headache attributed to spontaneous low CSF pressure (previously defined as spontaneous intracranial hypotension) is still a matter of debate. Epidural blood patch is considered the most effective treatment. However, pharmacological strategies may be considered before blood patch. We report three patients with headache attributed to spontaneous low CSF pressure that were successfully treated with oral prednisone. Additional studies may be useful to prove the effectiveness of corticosteroids in this syndrome.

Miller Fisher syndrome associated with Burkitt's lymphoma

Safety and efficacy of recombinant human alpha-galactosidase replacement therapy in Fabry’s disease. New England Journal of Medicine 2001; 2001; 345: 9–16. 4. Schiffmann R, Kopp JB, Austin HA III, et al. Enzyme replacement therapy in Fabry disease: a randomized controlled trial. JAMA 2001; 285: 2743–2749. 5. Sampietro T, Tuoni M, Ferdeghini M, et al. Plasma cholesterol regulates soluble cell adhesion molecule expression in familial hypercholesterolemia. Circulation 1997; 96: 1381–1385. 6. DeGraba T, Azhar S, Dignat-George F, Brown E, et al. Profile of endothelial and leukocyte activation in Fabry patients. Annals of Neurology 2000; 47: 229–233.

Attachment styles and headache

The internal working model on attachment dimensions changes with significant emotional experiences. The purpose of this study was to evaluate if and how the internal working models correlate with primary headaches. Attachment dimensions of subjects suffering from primary headaches were studied. One hundred and fourteen subjects [68 with migraine, 23 with tension–type headache (according to ICHD–I criteria), 23 with chronic daily headache (according to Silberstein’s criteria)], were studied and compared with a control group of 57 subjects (matched in sex, age and social level) not suffering from any primary headache. Attachment dimensions were investigated using the Adult Attachment Questionnaire (AAQ) and the Attachment Style Questionnaire (ASQ). Headache sufferers seem to be characterised by attachment styles of the “insecure” type. In particular they seem to feel extremely ill at ease if there is an expectation of reduction of interpersonal distance.

The 1246G-->A polymorphism of the HCRTR2 gene is not associated with migraine.

Studies in experimental animals have suggested that the hypocretin/orexin system may be involved in migraine pathophysiology. Using a case-control design study, we genotyped 246 migraine patients and 239 healthy controls for the 1246G→A polymorphism of the hypocretin receptor 2 (HCRTR2) gene. Genotypic and allelic frequencies of the examined polymorphism were similarly distributed between cases and controls (χ2 = 2.22, P = 0.14 and χ2 = 2.45, P = 0.29, respectively). When different migraine subgroups were compared (migraine with aura vs. migraine without aura and episodic vs. chronic migraine) no significant difference was found. Comparison of the clinical features of the disease with the 1246G→A genotypes showed no significant difference. Our data suggest that the HCRTR2 gene is not a genetic risk factor in migraine.

Haemochromatosis gene (HFE) polymorphisms and migraine: an association study

Several studies have suggested that iron metabolism may be involved in the pathogenesis of migraine. Using a case-control design, we performed an association study in a cohort of Italian migraine patients to evaluate whether a particular allele or genotype of the haemochromatosis gene (HFE) would modify the occurrence and clinical features of the disease. We genotyped 256 migraine patients and 237 healthy age-, sex- and ethnicity-matched controls for the C282Y and H63D polymorphisms of the HFE gene. Phenotype and allele frequencies of both polymorphisms were similarly distributed in migraine patients and controls. The patients carrying the DD genotype of the H63D polymorphism showed a later age at onset of the disease and an increased number of migraine attacks. Our data suggest that the HFE gene is not a major disease gene for migraine. However, the H63D polymorphism of the HFE gene may be considered a modifying genetic factor in migraine.