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.

Brain Changes in Responders vs. Non-Responders in Chronic Migraine: Markers of Disease Reversal.

The aim of this study was to identify structural and functional brain changes that accompanied the transition from chronic (CM; ≥15 headache days/month) to episodic (EM; <15 headache days/month) migraine following prophylactic treatment with onabotulinumtoxinA (BoNT-A). Specifically, we examined whether CM patients responsive to prophylaxis (responders; n = 11), as evidenced by a reversal in disease status (defined by at least a 50% reduction in migraine frequency and <15 headache days/month), compared to CM patients whose migraine frequency remained unchanged (non-responders; n = 12), showed differences in cortical thickness using surface-based morphometry. We also investigated whether areas showing group differences in cortical thickness displayed altered resting-state functional connectivity (RS-FC) using seed-to-voxel analyses. Migraine characteristics measured across groups included disease duration, pain intensity and headache frequency. Patient reports of headache frequency over the 4 weeks prior to (pre-treatment) and following (post-treatment) prophylaxis were compared (post minus pre) and this measure served as the clinical endpoint that determined group assignment. All patients were scanned within 2 weeks of the post-treatment visit. Results revealed that responders showed significant cortical thickening in the right primary somatosensory cortex (SI) and anterior insula (aINS), and left superior temporal gyrus (STG) and pars opercularis (ParsOp) compared to non-responders. In addition, disease duration was negatively correlated with cortical thickness in fronto-parietal and temporo-occipital regions in responders but not non-responders, with the exception of the primary motor cortex (MI) that showed the opposite pattern; disease duration was positively associated with MI cortical thickness in responders versus non-responders. Our seed-based RS-FC analyses revealed anti-correlations between the SI seed and lateral occipital (LOC) and dorsomedial prefrontal cortices (DMPFC) in responders, whereas non-responders showed increased connectivity between the ParsOp seed and LOC. Overall, our findings revealed distinct morphometric and functional brain changes in CM patients that reverted to EM following prophylactic treatment compared to CM patients that showed no change in disease status. Elucidating the CNS changes involved in disease reversal may be critical to discovering interventions that prevent or slow the progression of CM. Such changes may aid in the evaluation of treatments as well as provide markers for disease "de-chronification".

Our evolving understanding of migraine with aura.

Migraine aura consists of fully reversible focal neurologic symptoms that may precede or coexist with headache in a significant minority of migraine patients. Typical aura symptoms include visual, sensory, and language disturbances. The most recent International Classification of Headache Disorders, 3rd edition (beta version) has added other aura types such as brainstem localizing symptoms, lateralizing weakness, and monocular visual loss. Currently available data from animal models and functional neuroimaging in humans implicate cortical spreading depression (CSD) as the phenomenon underlying migraine aura. Ongoing study suggests that susceptibility to migraine aura and CSD may be genetically mediated. CSD appears to be a potential target for future development of migraine-specific preventive therapies.

Cough, exercise, and sex headaches.

Cough, exercise, and sex headaches are underrecognized distinct but related syndromes, triggered by rapid rises in intra-abdominal pressure. All may occur as a manifestation of a possible underlying, symptomatic etiology, and additional diagnostics should typically be pursued to rule out serious causes. Cough headaches may be more common in certain subgroups or settings. Based on recent epidemiologic data, exercise-related headache may be more common than previously thought. There is no evidence that different pain types in sexual headaches are distinct from a pathophysiologic standpoint. Each of these headache syndromes is reported to be responsive to indomethacin.