Dr. Burstein and Dr. Grosberg are the first recipients of the MRF Impact Award.

Final Report: Status Migrainosus

Published in Cephalagia: Unrecognized challenges of treating status migrainosus: An observational study,
January, 2020

Summary

Status migrainosus is a condition with limited epidemiological knowledge and no evidence-based guidelines for treatment or rational-driven assessment of successful treatment outcomes.  To fill this gap, we performed a prospective observational study in which we documented the effectiveness of 4 treatment approaches commonly used in a tertiary headache clinic.

Using a diary to capture treatment effects prospectively, we found that the overall success rate of rendering patients pain-free within 24 hours of treatment and maintaining the pain-free status for 48 hours was 22%.  This success rate was similar for dexamethasone (a steroidal anti-inflammatory) (31%), nerve blocks (24%), ketorolac (a non-steroidal anti-inflammatory) (11%) and naratriptan (a triptan) (11%). These success rates depend on time to remission, as the longer we allowed treatment to begin working and patients to become pain-free (i.e., 2, 12, 24, 48, 72, 96 hours), the more likely patients were to achieve and maintain a pain-free status for at least 48 hours. In contrast, the duration of maintaining the pain-free status (once achieved) was inversely related to the success rate. When the pain-free duration was increased from 1 to 7 days, the percentage of responders declined from 23% to 13% if remission was to be achieved within 24 hours, and from 53% to 18% if remission was to be achieved within 96 hours.

The overall success rate of 22% is disappointingly lower than expected given that patients made the effort to come to the clinic.  These findings demonstrate that current treatment approaches to terminating status migrainosus are not effective. They also call attention to the need to develop a more scientific approach to define a treatment response for status migrainosus.

Hypothesis vs. Findings

Our primary goal was to determine if it is possible to identify patients who respond to any one treatment and differentiate them from non-responders to the same treatment in the routine setting of a headache clinic.  Our secondary goal was to identify attributes of responders and nonresponders to any one treatment for an acute migraine attack that lasts 3 days or more. Our lead hypothesis was that different treatment approaches that are used routinely to terminate attacks that last 3 days or more will work differently in different patients as their mechanisms of action are different.  To test this hypothesis, we picked 4 treatments: nerve block (acts peripherally), naratriptan (5HT1b1d receptors agonist), dexamethasone (steroidal anti-inflammatory), and ketorolac (non-steroidal anti-inflammatory).  Only 22% of patients treated by these 4 approaches were classified as responders.  This low percentage prevented us from testing our hypothesis and reaching our goals.  Consequently, we focused on identifying the challenges of treating status migrainosus and the value of encouraging patients to seek help in the tertiary headache clinic if their self-administered treatment fails.

Unanswered Questions

Our findings raised questions about how to define a response to a status migrainosus treatment:

1. Time to remission – the proportion of patients achieving a pain-free status at 2, 12, 24, 48, 72 and 96 hours increased steadily from 2% to 8% to 23% to 37% to 43% to 53% respectively. These findings emphasize the need for a consensus definition on how much time can elapse before headache cessation can no longer be attributed to medication in status migrainosus. It is tempting to suggest that criteria for a positive response to status migrainosus treatment should allow 48 to 72 or even 96 hours for patients to become pain-free. While mechanistically it might make sense, clinically it is problematic as it introduces the possibility that the treated headache may have ended spontaneously.
2. Duration of remission – the proportion of patients whose pain-free status was sustained for 1, 2 and 3 days remained stable but declined steadily in days 4, 5, 6 and 7. These findings raise the possibility that the sustained pain-free duration of 1, 2, or 3 days should be considered in the definition of responders. We interpret the steady decline in the proportion of patients whose pain-free status is maintained for 4-7 days as those possibly experiencing the onset of new migraine attacks.
3. Standardized outcome measures -these findings point to a critical need to employ more standardized outcome measures to evaluate the effectiveness of status migrainosus treatments. An expert consensus should be developed on how to define treatment response for status migrainosus.

What This Research Means to You

We attempted to determine whether and why certain treatment approaches for status migrainosus work better for certain patients. We were unable to achieve this goal because very few patients achieved a headache-free status.  Given the burden of unplanned visits to the headache clinic, the disappointingly low rate of success raises concerns about the value of such visits.  Setting patients’ expectations correctly may ease post-treatment disappointment.