OnabotulinumtoxinA in elderly patients with chronic migraine: insights from a real-life European multicenter study.

INTRODUCTION: Although migraine prevalence decreases with aging, some older patients still suffer from chronic migraine (CM). This study aimed to investigate the outcome of OnabotulinumtoxinA (OBT-A) as preventative therapy in elderly CM patients. METHODS: This is a post hoc analysis of real-life prospectively collected data at 16 European headache centers on CM patients treated with OBT-A over the first three treatment cycles (i.e., Cy1-3). We defined: OLD patients aged ≥ 65 years and nonOLD those < 65-year-old. The primary endpoint was the changes in monthly headache days (MHDs) from baseline to Cy 1-3 in OLD compared with nonOLD participants. The secondary endpoints were the responder rate (RR) ≥ 50%, conversion to episodic migraine (EM) and the changes in days with acute medication use (DAMs). RESULTS: In a cohort of 2831 CM patients, 235 were OLD (8.3%, 73.2% females, 69.6 years SD 4.7). MHDs decreased from baseline (24.8 SD 6.2) to Cy-1 (17.5 SD 9.1, p < 0.000001), from Cy-1 to Cy-2 (14.8 SD 9.2, p < 0.0001), and from Cy-2 to Cy-3 (11.9 SD 7.9, p = 0.001). DAMs progressively reduced from baseline (19.2 SD 9.8) to Cy-1 (11.9 SD 8.8, p < 0.00001), to Cy-2 (10.9 SD 8.6, p = 0.012), to Cy-3 (9.6 SD 7.4, p = 0.049). The 50%RR increased from 30.7% (Cy-1) to 34.5% (Cy-2), to 38.7% (Cy-3). The above outcome measures did not differ in OLD compared with nonOLD patients. CONCLUSION: In a population of elderly CM patients with a long history of migraine OBT-A provided a significant benefit, over the first three treatment cycles, as good as in non-old patients.

InterMiG: international differences in the therapeutic approach to migraine patients in specialized headache centers.

BACKGROUND: There is currently a wide therapeutic arsenal for migraine patients, without a single first-line preventive drug and we choose the different available alternatives taking into account comorbidities, national guidelines, previous treatments and personal experiences. Our objective was to evaluate the differences in the use of migraine treatments between neurologists from different countries. METHODS: This is a multi-centre observational study carried out by neurologists from specialized headache units in seven countries, retrospective with consecutive inclusion of all patients presenting with a migraine diagnosis, over a period of three months. RESULTS: A total of 734 patients were recruited but only 600 were considered in the analysis in order to homogenize the patient cohorts from countries: 200 Spain (ES), 100 Italy (IT), 85 Russia (RUS), 80 Germany (DE), 60 Portugal (PT), 45 Poland (PL) and 30 Australia (AU). 85.4 % of patients were women with a mean age of 42.6 ± 11.8 years. Considering previous and current preventive treatment, the order of use was: antidepressants (69.3 %), antiepileptic drugs (54.7 %), beta-blockers and antihypertensive drugs (49.7 %), OnabotulinumtoxinA (44.0 %) and others (36.2 %). Statistically significant differences were found between all pharmacological classes: antidepressants were commonly used in all countries, with the exception of Poland (AU: 76.7 %, IT: 71.0 %, DE: 60.0 %, PL: 31.1 %, PT: 71.7 %, RUS: 70.6 %, ES: 78.5 %; p < 0.0001); antiepileptic drugs were more frequently prescribed in Portugal, Australia and Spain (AU: 73.3 %, IT: 40.0 %, DE: 37.5 %, PL: 48.9 %, PT: 85.0 %, RUS: 29.4 % and ES: 69.0 %; p < 0.0001); beta-blockers and antihypertensive drugs were frequently used in all countries except Italy (AU: 60.0 %, IT: 14.0 %, DE: 53.8 %, PL: 48.9 %, PT: 68.3 %, RUS: 49.4 % and ES: 59.0 %; p < 0.0001); BTX-A were predominately used in Spain, Italy and Australia (AU:56.7 %, IT:58.0 %, DE:20.0 %, PL: 42.2 %, PT: 26.7 %, RUS: 24.7 % and ES: 58.5 %; p < 0.0001) and others were most frequently used in Poland (AU: 0.0 %, IT: 19.0 %, DE: 42.5 %, PL: 95.6 %, PT: 31.7 %, RUS: 3.5 % and ES: 49.5 %; p < 0.0001). If only patients without comorbidities are considered (200/600), statistically differences between countries persist in all preventive treatments. CONCLUSIONS: There is heterogeneity in the choice of preventive treatment between different countries. Prospective comparative studies of the different oral and subcutaneous alternatives would help to create a global therapeutic algorithm that would guarantee the best option for our patients.

Headache and pregnancy: a systematic review.

This systematic review summarizes the existing data on headache and pregnancy with a scope on clinical headache phenotypes, treatment of headaches in pregnancy and effects of headache medications on the child during pregnancy and breastfeeding, headache related complications, and diagnostics of headache in pregnancy. Headache during pregnancy can be both primary and secondary, and in the last case can be a symptom of a life-threatening condition. The most common secondary headaches are stroke, cerebral venous thrombosis, subarachnoid hemorrhage, pituitary tumor, choriocarcinoma, eclampsia, preeclampsia, idiopathic intracranial hypertension, and reversible cerebral vasoconstriction syndrome. Migraine is a risk factor for pregnancy complications, particularly vascular events. Data regarding other primary headache conditions are still scarce. Early diagnostics of the disease manifested by headache is important for mother and fetus life. It is especially important to identify "red flag symptoms" suggesting that headache is a symptom of a serious disease. In order to exclude a secondary headache additional studies can be necessary: electroencephalography, ultrasound of the vessels of the head and neck, brain MRI and MR angiography with contrast ophthalmoscopy and lumbar puncture. During pregnancy and breastfeeding the preferred therapeutic strategy for the treatment of primary headaches should always be a non-pharmacological one. Treatment should not be postponed as an undermanaged headache can lead to stress, sleep deprivation, depression and poor nutritional intake that in turn can have negative consequences for both mother and baby. Therefore, if non-pharmacological interventions seem inadequate, a well-considered choice should be made concerning the use of medication, taking into account all the benefits and possible risks.

Declining incidence of intracerebral hemorrhage over two decades in a population-based study.

BACKGROUND AND PURPOSE: The incidence and case-fatality rate (CFR) of primary intracerebral hemorrhage (PICH) over two decades were assessed in a prospective population-based study. METHODS: Cases of incident first-ever PICH were recorded over a 2-year period (2011-2012) from multiple sources in the district of L'Aquila, central Italy. Included patients were followed up to 1 year after the event to ascertain CFRs. Current data were compared with those previously collected from 1994 through 1998. RESULTS: In all, 115 patients (52 men; 45.2%) with a first-ever PICH were included. Mean age ± SD was 77.4 ± 11.8 years. The hemorrhage was lobar in 43 (37.4%) patients, deep in 56 (48.7%), in the posterior fossa in 11 (9.6%) and intraventricular or multiple localized in five (4.3%). Crude annual incidence rate was 19.3 per 100 000 and 14.8 per 100 000 when standardized to the 2011 European population, indicating a 48% reduction comparing data of 2011-2012 to those of 1994-1998 (incidence rate ratio 0.52; 95% confidence interval 0.43-0.64; P < 0.001). In 2011-2012, the 7-day CFR was 27.8%, the 30-day CFR was 42.6% and the 1-year CFR was 52.2%; the 1-year standardized mortality ratio was 0.81 (95% confidence interval 0.63-1.04) compared with 1994-1998. CONCLUSIONS: The annual incidence rate of PICH was lower than that found two decades before and close to the rates recently found in other western countries. Data also indicated a non-significant trend towards a decrease in mortality, which nonetheless remained high, pointing to the need for more appropriate treatments in order to reduce PICH severity and mortality.

Migraine and risk of ischaemic heart disease: a systematic review and meta-analysis of observational studies.

BACKGROUND AND PURPOSE: Several studies have assessed the risk of ischaemic heart diseases in migraineurs, drawing different conclusions. To define and update the issue, a systematic review and meta-analysis of the available observational studies was performed. METHODS: PubMed and EMBASE were systematically searched up to April 2014 for observational studies dealing with the risk of any form of ischaemic heart disease in migraineurs. Studies assessing migraine as exposure and several types of ischaemic heart disease as outcomes were included in the analysis. A random effects model was used to pool the effect sizes. RESULTS: Out of 3348 records, 15 studies (one case-control, one cross-sectional and 13 cohort studies) were identified and were included in the meta-analysis. The pooled analysis indicated an increased risk of myocardial infarction (pooled adjusted effect estimate 1.33, 95% confidence interval 1.08-1.64; P = 0.007) and of angina (pooled adjusted effect estimate 1.29, 95% confidence interval 1.17-1.43; P < 0.0001) in migraineurs compared to non-migraineurs. CONCLUSIONS: Based on our data indicating an association of migraine with myocardial infarction and angina and on previous data showing an association of migraine, and particularly migraine with aura, with an increased risk for stroke, migraine can be appropriately considered an overall risk factor for cardiovascular diseases.

Insulin resistance in migraineurs: results from a case-control study.

OBJECTIVES: Several studies have suggested an association between migraine and insulin resistance (IR) without adequately addressing the issue according to migraine type. We assessed IR in subjects with migraine with aura (MwA) and migraine without aura (MwoA) to estimate the consistency of the possible association. METHODS: In a case-control study we included case subjects with MwA and MwoA, who were consecutively selected from those referred to our Regional Headache Center from September 2011 to February 2013, and age-matched control subjects selected using general practitioners' databases. IR was calculated by means of the homeostatic model assessment of IR (HOMA-IR), ß-cell function (HOMA-B), and the quantitative insulin sensitivity check index (QUICKI) measuring glucose and insulin values in a blood sample collected in the morning after overnight fasting. Data regarding anthropometric measures, comorbidity risk factors, and migraine characteristics were also recorded. RESULTS: We recruited 50 case subjects with MwA (38 women) and 50 with MwoA (40 women) and 50 control subjects (40 women). Proportions of arterial hypertension, cigarette smoking, hypercholesterolemia, use of oral contraceptives, and mean values of the body mass index (BMI) were similar in the three groups. We found significantly different glucose values among and within groups considering case subjects with MwA and MwoA and control subjects (4.9 ± 0.6 vs 4.7 ± 0.5 vs 4.6 ± 0.5 mmol/l; P = 0.018) in the absence of any difference in insulin (53.1 ± 24.0 vs 56.7 ± 34.4 vs 53.8 ± 24.4 pmol/l; P = 0.811), HOMA-IR (1.6 ± 0.8 vs 1.7 ± 1.0 vs 1.6 ± 0.7; P = 0.765), HOMA-B (121.4 ± 71.1 vs 149.2 ± 93.8 vs 162.8 ± 109.7; P = 0.107), and QUICKI (0.36 ± 0.03 vs 0.37 ± 0.03 vs 0.37 ± 0.03; P = 0.877) values. The logistic regression model showed increased odds of MwA in subjects exposed to the highest tertile of glucose values. This association was confirmed in the adjusted model, in which case subjects with MwA were compared with those with MwoA but not with control subjects. CONCLUSIONS: In contrast to what has been shown by the majority of the available studies, the results of our study do not support the association of migraine with IR. As our study was not population-based and several patients had low disease activity, these findings need further confirmation.