Cough, Exertional, and Sex Headaches.

In this article, the authors review the most common presentations of cough and exertional headaches and headaches associated with sexual activity. The authors elaborate on the most commonly described etiologies and identify those which are most critical to treat. The authors outline the recommendations for further evaluation and discuss effective treatment modalities for each headache type.

Pathophysiology of migraine aura.

Migraine aura occurs in about a third of patients with migraine and consists of a group of transient focal neurological symptoms that appear from 5 to 60min and then resolve prior to or in the early phase of a migraine headache attack. Migraine auras may consist of visual, language, unilateral sensory, or motor symptoms. There has been considerable debate as to the origins of the migrainous aura. Investigations during physiologically induced visual auras suggest that the phenomenon of cortical spreading depression or its human equivalent underpins the migraine aura. Single gene defects have been linked to relatively rare forms of the motor subtypes of aura known as familial hemiplegic migraine (FHM). These include CACNA1A (FHM1), ATP1A2 (FHM2), and SCN1A (FHM3). In the familial hemiplegic forms of migraine, the more typical forms of aura are almost always also present. Despite ample epidemiological evidence of increased heritability of migraine with aura compared to migraine without aura, identification of the specific variants driving susceptibility to the more common forms of aura has been problematic thus far. In the first genome-wide association study (GWAS) that focused migraine with aura, a single SNP rs835740 reached genome-wide significance. Unfortunately, the SNP did show statistical significance in a later meta-analysis which included GWAS data from subsequent studies. Here, we review the clinical features, pathophysiological theories, and currently available potential evidence for the genetic basis of migraine aura.

OnabotulinumtoxinA in chronic migraine: is the response dose dependent?

BACKGROUND: OnabotulinumtoxinA has been widely used for control of chronic migraine. The aim of the current study was to evaluate the efficacy of different doses of the onabotulinumtoxinA therapy in patients with chronic migraine. METHODS: This is a retrospective paired comparison study on patients with chronic migraine who received at least 3 rounds of 150 units of onabotulinumtoxinA followed by at least 3 rounds of 200 units of onabotulinumtoxinA. The data from the patient-reported questionnaires about headache days, severe headache days and wearing off periods were reviewed. RESULTS: A total of 175 patients were included in this study. The headache days and severe headache days decreased from 13.62 ± 10.79 and 5.88 ± 6.73 to 11.02 ± 10.61and 4.01 ± 4.89 days, after increase in the onabotulinumtoxinA dose, respectively (P < 0.001 for both comparisons). The favorable effect of the 200 units compared to the 150 units of the onabotulinumtoxinA, was independent from the headache location and the duration of the onabotulinumtoxinA 150 units therapy; and persisted as patients continued to receive the higher dose of onabotulinumtoxinA. Increase in the onabotulinumtoxinA dose was also associated with a decreased wearing off period (P < 0.05). CONCLUSION: We found that increase in the onabotulinumtoxinA is associated with fewer headache and severe headache days. Future randomized clinical trials are needed to confirm the dose-dependent response to onabotulinumtoxinA.

Determinants of pain interference and headache impact in patients who have chronic migraine with medication overuse: Results from the MOTS trial.

OBJECTIVE: "Pain interference" and "headache impact" refer to negative consequences that pain and headache have on one's life. This study investigated determinants of these negative impacts in a large patient cohort who have chronic migraine with medication overuse. METHODS: Six hundred and eleven adults were enrolled from 34 headache, neurology, and primary care clinics. Negative consequences of chronic migraine with medication overuse were determined using the Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference 6b questionnaire and the Headache Impact Test 6. Relationships between PROMIS-6b and Headache Impact Test 6 scores with demographics, headache characteristics, medication use, anxiety symptoms, and depression symptoms were assessed with linear regression. Elastic Net regression was used to develop a multiple regression model. RESULTS: PROMIS-6b T-Scores averaged 65.2 (SD 5.4) and Headache Impact Test 6 scores averaged 65.0 (SD 5.3), indicating severe negative consequences of chronic migraine with medication overuse. Chronic migraine with medication overuse interfered with enjoyment of life, concentration, daily activities, doing tasks away from home, and socializing. Depression symptom severity had the strongest relationship with pain interference and headache impact. Moderate-to-severe headache frequency, headache intensity, and anxiety symptoms were also associated with pain interference and headache impact. CONCLUSIONS: Chronic migraine with medication overuse is associated with substantial negative consequences, the extent of which is most strongly related to depression symptoms.

Genetic variants related to successful migraine prophylaxis with verapamil.

BACKGROUND: Currently, there is no biologically based rationale for drug selection in migraine prophylactic treatment. METHODS: To investigate the genetic variation underlying treatment response to verapamil prophylaxis, we selected 225 patients from a longitudinally established, deeply phenotyped migraine database (N = 5983), and collected uninterrupted quantitated verapamil treatment response data and DNA for these 225 cases. We recorded the number of headache days in the four weeks preceding treatment with verapamil and for four weeks, following completion of a treatment period with verapamil lasting at least five weeks. Whole-exome sequencing (WES) was applied to a discovery cohort consisting of 21 definitive responders and 14 definitive non-responders, and the identified single nucleotide polymorphisms (SNPs) showing significant association were genotyped in a separate confirmation cohort (185 verapamil treated patients). Statistical analysis of the WES data from the discovery cohort identified 524 SNPs associated with verapamil responsiveness (p < 0.01); among them, 39 SNPs were validated in the confirmatory cohort (n = 185) which included the full range of response to verapamil from highly responsive to not responsive. RESULTS: Fourteen SNPs were confirmed by both percentage and arithmetic statistical approaches. Pathway and protein network analysis implicated myo-inositol biosynthetic and phospholipase-C second messenger pathways in verapamil responsiveness, emphasizing the earlier pathogenic understanding of migraine. No association was found between genetic variation in verapamil metabolic enzymes and treatment response. CONCLUSION: Our findings demonstrate that genetic analysis in well-characterized subpopulations can yield important pharmacogenetic information pertaining to the mechanism of anti-migraine prophylactic medications.

Aura and Other Neurologic Dysfunction in or with Migraine.

PREMISE: Migraine can present with a wide range of neurological symptoms. PROBLEM: Based on currently available data, the symptoms of typical migraine aura are most likely related to cortical spreading depression (CSD), and evidence supports that CSD can lead to trigeminovascular activation resulting in the headache phase of migraine. POTENTIAL SOLUTION: An alternative diagnosis to migraine aura should be considered if migrainous headaches present with transient neurological symptoms that have features inconsistent with aura.

A touchy subject: an assessment of cutaneous allodynia in a chronic migraine population.

BACKGROUND: Cutaneous allodynia (CA) is a common feature of migraine, which has a complex underlying pathophysiology that is not well understood. In addition to pain, photophobia, phonophobia, osmophobia, nausea, and vomiting, CA can contribute to the overall disability caused by migraine. The presence of CA can be established via a validated questionnaire. Validated questionnaires and other tests are rarely performed in clinical practice. As such, current prevalence estimates for CA may be an underestimation. METHODS: Utilizing a validated questionnaire, we assessed the presence of CA in consecutive patients (n=44) presenting with chronic migraine at a tertiary headache center. RESULTS: CA appears to be quite prevalent, at ~90%, among female patients with chronic migraine. CONCLUSION: CA prevalence in chronic migraine may be underestimated in the literature, and larger studies may better demonstrate a more accurate estimate of its prevalence.