Environmental risk factors and clinical phenotype in familial and sporadic primary blepharospasm.

BACKGROUND: Although environmental and genetic factors may contribute to the etiology of blepharospasm, their relative contribution in causing familial and sporadic blepharospasm is unknown. METHODS: First-degree relatives of 122 patients with primary blepharospasm were examined with a validated 2-step diagnostic procedure, including a screening questionnaire and examination of some relatives. Examiners were blinded to the questionnaire data for family history of probands. Data for demographic and clinical features, prior ophthalmologic complaints, and nondecaffeinated coffee intake were collected from probands before family investigation. RESULTS: Dystonia was diagnosed in 27 relatives from 23 families (20% rate of family history for dystonia). No significant differences were found between familial and sporadic cases in the frequency of coffee drinking and eye diseases or in sex, age at onset, or tendency to spread. Multivariable conditional logistic analysis testing of 67 case patients and 127 family-matched unaffected siblings yielded a significant positive association between blepharospasm and prior eye diseases (adjusted odds ratio [OR] 2.5; 95% confidence interval [CI] 1.1-6.1; p = 0.03) and a significant inverse association between case status and ever coffee drinking (adjusted OR 0.23; 95% CI 0.1-0.8; p = 0.02). CONCLUSIONS: The new information from this large family-based study on primary blepharospasm strongly supports eye diseases and coffee as risk factors for blepharospasm. The finding that the 2 environmental exposures exerted a similar influence on familial and sporadic blepharospasm, together with the convergent phenotypic expression in familial and sporadic cases, implies that familial and sporadic blepharospasm probably share a common etiologic background.

Anti-basal ganglia antibodies and Tourette's syndrome: a voxel-based morphometry and diffusion tensor imaging study in an adult population.

Anti-basal ganglia antibodies (ABGAs) have been suggested to be a hallmark of autoimmunity in Gilles de la Tourette's syndrome (GTS), possibly related to prior exposure to streptococcal infection. In order to detect whether the presence of ABGAs was associated with subtle structural changes in GTS, whole-brain analysis using independent sets of T(1) and diffusion tensor imaging MRI-based methods were performed on 22 adults with GTS with (n = 9) and without (n = 13) detectable ABGAs in the serum. Voxel-based morphometry analysis failed to detect any significant difference in grey matter density between ABGA-positive and ABGA-negative groups in caudate nuclei, putamina, thalami and frontal lobes. These results suggest that ABGA synthesis is not related to structural changes in grey and white matter (detectable with these methods) within frontostriatal circuits.

Influence of coffee drinking and cigarette smoking on the risk of primary late onset blepharospasm: evidence from a multicentre case control study.

Prior coffee and smoking habits were investigated in a multicentre case control study involving 166 patients presenting with primary late onset blepharospasm (BSP), 228 hospital control patients with primary hemifacial spasm and 187 population control subjects from five Italian centres. Information on age at disease onset, smoking and coffee drinking status at the reference age and average number of cups of coffee drunk/cigarettes smoked per day reached high and similar test-retest reproducibility in case and control patients. Unadjusted logistic regression analysis yielded a significant inverse association of prior coffee drinking and cigarette smoking with case status for the control groups. After adjustment for age, sex, referral centre, disease duration, years of schooling and ever coffee drinking/cigarette smoking, as appropriate, the smoking estimate lacked significance whereas the association of coffee intake and BSP did not (cases vs hospital control patients: OR 0.37 (95% CI 0.20 to 0.67); cases vs population control subjects: OR 0.44 (95% CI 0.23 to 0.85)). The strength of the inverse association between BSP and coffee intake tended to increase with the average number of cups drunk per day. There was a significant correlation between age of BSP onset and number of cups per day (adjusted regression coefficient 1.73; p = 0.001) whereas no correlation was found with number of packs of cigarettes per day. Coffee drinking may be inversely associated with the development of primary BSP and this association may partly depend on the amount consumed.

Interferon beta-1a downregulates TNFalpha-induced intercellular adhesion molecule 1 expression on brain microvascular endothelial cells through a tyrosine kinase-dependent pathway.

TNFalpha (100 U/ml, 24 h) upregulated intercellular adhesion molecule 1 (ICAM1) expression on brain microvascular endothelial cell (BMEC) culture. The tyrosine kinase (TK) inhibitor genestein (100 microgram/ml), the protein kinase C (PKC) inhibitor staurosporin (1 nM), and interferon (IF) beta-1a (1000 U/ml) antagonized TNFalpha effect. When an ineffective dose of IFbeta-1a (100 U/ml) was challenged with ineffective doses of either genestein (10 microgram/ml) or staurosporin (0.1 nM), the combination IFbeta-1a-genestein significantly reduced TNFalpha-induced ICAM1 expression whereas IFbeta-1a-staurosporin did not. These findings indicate that a TK- rather than a PKC-dependent mechanism is involved in the modulation of TNFalpha response by IFbeta-1a on BMECs.