Treatment of Cluster Headache in Pregnancy and Lactation

Cluster headache (CH) is a neurovascular headache syndrome characterized by headache attacks that occur with a circadian and circannual periodicity. The calculated prevalence of CH in reproductive-aged women is 7.5 of 100,000 women. Although data suggest that CH during pregnancy is a relatively rare condition, when it does occur, attacks remain unchanged in character and severity in the majority of patients. Thus, treatment of CH in pregnant and lactating women may remain a significant therapeutic challenge. This manuscript briefly reviews the epidemiology of CH in women, and then focuses on treatment options for both acute and preventative management of CH in pregnant and lactating women

Migraine and estrogen

The aim is to systematically and critically review the relationship between migraine and estrogen, the predominant female sex hormone, with a focus on studies published in the last 18 months

Agreement of self-reported physician diagnosis of migraine with international classification of headache disorders-II migraine diagnostic criteria in a cross-sectional study of pregnant women

Background: Migraine, a common chronic-intermittent disorder among reproductive age women, has emerged as a novel risk factor for adverse perinatal outcomes. Diagnostic reliability of self-report of physician-diagnosed migraine has not been investigated in pregnancy cohort studies. We investigated agreement of self-report of physician-diagnosed migraine with the diagnostic criteria promoted by the International Classification of Headache Disorders, 2nd edition (ICHD-II). Methods: The cross-sectional study was conducted among 500 women who provided information on a detailed migraine questionnaire that allowed us to apply all ICHD-II diagnostic criteria. Results: Approximately 92% of women reporting a diagnosis of migraine had the diagnosis between the ages of 11 and 40 years (40 years 1.0%). We confirmed self-reported migraine in 81.6% of women when applying the ICHD-II criteria for definitive migraine (63.1%) and probable migraine (18.5%). Conclusion: There is good agreement between self-reported migraine and ICHD-II-based migraine classification in this pregnancy cohort. We demonstrate the feasibility of using questionnaire-based migraine assessment according to full ICHD-II criteria in epidemiological studies of pregnant women

Defining Refractory Migraine: Results of the RHSIS Survey of American Headache Society Members

To gauge consensus regarding a proposed definition for refractory migraine proposed by Refractory Headache Special Interest Section, and where its use would be most appropriate. Background.— Headache experts have long recognized that a subgroup of headache sufferers remains refractory to treatment. Although different groups have proposed criteria to define refractory migraine, the definition remains controversial. The Refractory Headache Special Interest Section of the American Headache Society developed a definition through a consensus process, assisted by a literature review and initial membership survey. Design.— A 12-item questionnaire was distributed at the American Headache Society meeting in 2007 during a platform session and at the Refractory Headache Special Interest Section symposium. The same questionnaire was subsequently sent to all American Headache Society members via e-mail. A total of 151 responses from AHS members form the basis of this report. The survey instrument was designed using Survey Monkey. Frequencies and percentages of the survey were used to describe survey responses. Results.— American Headache Society members agreed that a definition for refractory migraine is needed (91%) that it should be added to the International Classification of Headache Disorders-2 (86%), and that refractory forms of non-migraine headache disorders should be defined (87%). Responders believed a refractory migraine definition would be of greatest value in selecting patients for clinical drug trials. The current refractory migraine definition requires a diagnosis of migraine, interference with function or quality of life despite modification of lifestyle factors, and adequate trials of acute and preventive medicines with established efficacy. The proposed criteria for the refractory migraine definition require failing 2 preventive medications to meet the threshold for failure. Although 42% of respondents agreed with the working definition of refractory migraine, 43% favored increasing the number to 3 (50%) or 4 (26%) preventive treatment failures. When respondents were asked if they felt that the proposed definition was appropriate to select patients for invasive procedures (patent foramen ovale repair or stimulators) only 44% agreed. Conclusions.— There is a consensus for a need for a definition for refractory migraine and that it should be added to the International Classification of Headache Disorder-2. There was also general agreement by the responders that refractory forms of non-migraine headache disorders should be defined.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72860/1/j.1526-4610.2009.01370.x.pd

Migraine and the risk of post-traumatic stress disorder among a cohort of pregnant women

Background Individually both migraine and post-traumatic stress disorder (PTSD) prevalence estimates are higher among women. However, there is limited data on the association of migraine and PTSD in women during pregnancy. Methods We examined the association between migraine and PTSD among women attending prenatal clinics in Peru. Migraine was characterized using the International Classification of Headache Disorders (ICHD)-III beta criteria. PTSD was assessed using the PTSD Checklist-Civilian Version (PCL-C). Multivariable logistic regression analyses were performed to estimate odds ratios (OR) and 95% confidence intervals (CI) after adjusting for confounders. Results Of the 2922 pregnant women included, 33.5% fulfilled criteria for any migraine (migraine 12.5%; probable migraine 21.0%) and 37.4% fulfilled PTSD criteria. Even when controlling for depression, women with any migraine had almost a 2-fold increased odds of PTSD (OR: 1.97; 95% CI: 1.64–2.37) as compared to women without migraine. Specifically, women with migraine alone (i.e. excluding probable migraine) had a 2.85-fold increased odds of PTSD (95% CI: 2.18–3.74), and women with probable migraine alone had a 1.61-fold increased odds of PTSD (95% CI: 1.30–1.99) as compared to those without migraine, even after controlling for depression. In those women with both migraine and comorbid depression, the odds of PTSD in all migraine categories were even further increased as compared to those women without migraine. Conclusion In a cohort of pregnant women, irrespective of the presence or absence of depression, the odds of PTSD is increased in those with migraine. Our findings suggest the importance of screening for PTSD, specifically in pregnant women with migraine.This research was supported by awards from the National Institutes of Health (NIH), National Institute of Minority Health and Health Disparities (T37-MD- 001449), and the Eunice Kenney Shriver National Institute of Child Health and Human Development (R01-HD-059835). The NIH had no further role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.Revisión por pare

Migraine and white matter hyperintensities: The ARIC MRI study

OBJECTIVE: Migraine is associated with white matter hyperintensities (WMH) cross-sectionally, but its effect on WMH progression is uncertain. METHODS: Participants in the Atherosclerosis Risk in Communities cohort study (n = 10,924) completed a standardized headache questionnaire between 1993 and 1995. A subset of participants (n = 1,028) received 2 MRIs 8 to 12 years apart: once at the time of headache ascertainment, and again from 2004 to 2006. WMH were quantified using both a visually graded score (0-9) and semiautomated volumetric analysis. Linear and logistic regression models adjusted for age, sex, and other vascular risk factors were constructed. RESULTS: Individuals who had migraine without aura were cross-sectionally associated with an 87% greater odds of having a WMH score ≥3 than individuals without headache (adjusted odds ratio = 1.87; 95% confidence interval [CI]: 1.04, 3.37). Participants with migraine had an average of 2.65 cm(3) more WMH than those without headache (95% CI: 0.06, 5.24). However, there was no significant difference in WMH progression over the study period between individuals with and without migraine (1.58 cm(3) more progression for individuals with migraine compared to those without; 95% CI: -0.37, 3.53). CONCLUSION: Migraine is associated with WMH volume cross-sectionally but not with WMH progression over time. This suggests that the association between migraine and WMH is stable in older age and may be primarily attributable to changes occurring earlier in life, although further work is needed to confirm these findings

Adiponectin and leptin levels in migraineurs in the Atherosclerosis Risk in Communities Study

OBJECTIVE: To evaluate adiponectin and leptin levels in older men and women with migraine. METHODS: Fasting total and high molecular weight (HMW) adiponectin and leptin levels were evaluated in a case-cohort study of nondiabetic older migraine and nonmigraine control participants from the ongoing, longitudinal, general population, Atherosclerosis Risk in Communities Study at visit 1 (1987-1989). A standardized headache questionnaire was completed at visit 3 (1993-1995). Logistic regression models adjusted for age, sex, race, center, body mass index, and fasting glucose were used to evaluate the association of each adipocytokine with migraine. RESULTS: Of the 981 participants, the mean age at baseline was 52.8 years (SE 0.3); 131 fulfilled migraine criteria. Crude, mean total adiponectin levels were greater in men and women with migraine (8.1 µg/mL, SE 0.5) as compared to those without migraine (7.0 µg/mL, SE 0.2) (p = 0.031). After adjustments, the odds of migraine were increased by 88% with each SD increase in total adiponectin in men (odds ratio [OR] 1.86; 95% confidence interval [CI] 1.15, 3.01; p = 0.011), but not in women (OR 1.05; 95% CI 0.80, 1.37; p = 0.728; p interaction = 0.029). Similar results were demonstrated for HMW adiponectin. Crude and adjusted leptin levels were not associated with migraine. CONCLUSIONS: Although crude, total adiponectin levels were higher in older men and women with migraine than controls, after adjustments, the prevalence of migraine was significantly associated with total adiponectin only in older men, suggesting the association may be confounded or absent in older women. Leptin was not associated with migraine in older men or women

RNA polymerase II stalling promotes nucleosome occlusion and pTEFb recruitment to drive immortalization by Epstein-Barr virus

Epstein-Barr virus (EBV) immortalizes resting B-cells and is a key etiologic agent in the development of numerous cancers. The essential EBV-encoded protein EBNA 2 activates the viral C promoter (Cp) producing a message of ~120 kb that is differentially spliced to encode all EBNAs required for immortalization. We have previously shown that EBNA 2-activated transcription is dependent on the activity of the RNA polymerase II (pol II) C-terminal domain (CTD) kinase pTEFb (CDK9/cyclin T1). We now demonstrate that Cp, in contrast to two shorter EBNA 2-activated viral genes (LMP 1 and 2A), displays high levels of promoter-proximally stalled pol II despite being constitutively active. Consistent with pol II stalling, we detect considerable pausing complex (NELF/DSIF) association with Cp. Significantly, we observe substantial Cp-specific pTEFb recruitment that stimulates high-level pol II CTD serine 2 phosphorylation at distal regions (up to +75 kb), promoting elongation. We reveal that Cp-specific pol II accumulation is directed by DNA sequences unfavourable for nucleosome assembly that increase TBP access and pol II recruitment. Stalled pol II then maintains Cp nucleosome depletion. Our data indicate that pTEFb is recruited to Cp by the bromodomain protein Brd4, with polymerase stalling facilitating stable association of pTEFb. The Brd4 inhibitor JQ1 and the pTEFb inhibitors DRB and Flavopiridol significantly reduce Cp, but not LMP1 transcript production indicating that Brd4 and pTEFb are required for Cp transcription. Taken together our data indicate that pol II stalling at Cp promotes transcription of essential immortalizing genes during EBV infection by (i) preventing promoter-proximal nucleosome assembly and ii) necessitating the recruitment of pTEFb thereby maintaining serine 2 CTD phosphorylation at distal regions

A Cyclin-Dependent Kinase that Promotes Cytokinesis through Modulating Phosphorylation of the Carboxy Terminal Domain of the RNA Pol II Rpb1p Sub-Unit

In Schizosaccharomyces pombe, the nuclear-localized kinase, Lsk1p, promotes cytokinesis by positively regulating the Septation Initiation Network (SIN). Although a member of the cyclin-dependent kinase (CDK) family, neither a cyclin partner nor a physiological target has been identified. In this report we identify a cyclin, Lsc1p, that physically interacts and co-localizes with Lsk1p. Furthermore, lsk1Δ, lsc1Δ, as well as kinase-dead lsk1-K306R mutants, display highly similar cytokinesis defects. Lsk1p is related to CDKs that phosphorylate the carboxy-terminal domain (CTD) of the largest sub-unit of RNA polymerase II (Rpb1p). Interestingly, we find that Lsk1p and Lsc1p are required for phosphorylation of Ser-2 residues found in the heptad repeats of the CTD. To determine if Rpb1p could be a physiological target, we replaced the native rpb1 gene with a synthetic gene encoding a Rpb1p protein in which Ser-2 was substituted with the non-phosphorylatable amino-acid alanine in all heptads. Cells carrying this allele were similar to lsk1Δ mutants: They were viable, displayed genetic interactions with the SIN, and were unable to complete cytokinesis upon perturbation of the cell division machinery. We conclude that Ser-2 phosphorylation of the CTD heptads plays a novel physiological role in the regulation of cytokinesis

miR-198 Inhibits HIV-1 Gene Expression and Replication in Monocytes and Its Mechanism of Action Appears To Involve Repression of Cyclin T1

Cyclin T1 is a regulatory subunit of a general RNA polymerase II elongation factor known as P-TEFb. Cyclin T1 is also required for Tat transactivation of HIV-1 LTR-directed gene expression. Translation of Cyclin T1 mRNA has been shown to be repressed in human monocytes, and this repression is relieved when cells differentiate to macrophages. We identified miR-198 as a microRNA (miRNA) that is strongly down-regulated when monocytes are induced to differentiate. Ectopic expression of miR-198 in tissue culture cells reduced Cyclin T1 protein expression, and plasmid reporter assays verified miR-198 target sequences in the 3′ untranslated region (3′UTR) of Cyclin T1 mRNA. Cyclin T1 protein levels increased when an inhibitor of miR-198 was transfected into primary monocytes, and overexpression of miR-198 in primary monocytes repressed the normal up-regulation of Cyclin T1 during differentiation. Expression of an HIV-1 proviral plasmid and HIV-1 replication were repressed in a monocytic cell line upon overexpression of miR-198. Our data indicate that miR-198 functions to restrict HIV-1 replication in monocytes, and its mechanism of action appears to involve repression of Cyclin T1 expression