When a Migraine Lasts for Days: Gaining a Sense of the Scope of the Problem

A new study provides the first population-based estimate of the incidence of status migrainosus.

Status migrainosus (SM) is a serious complication of migraine in which the associated pain and non-pain symptoms are unremitting and debilitating for more than 72 hours. Considering that SM entails an increased risk of suicide and frequent hospitalization, perhaps it is surprising that epidemiological knowledge of this condition is lacking. A new study now corrects that deficiency with the first population-based estimate of the incidence of SM.

Using patient data from the Rochester Epidemiology Project, researchers led by Juliana VanderPluym, Mayo Clinic, Scottsdale, US, report an incidence rate of 26.6 per 100,000 person-years among residents of Olmsted County in the state of Minnesota, after adjusting for sex and age. The study, which included 237 cases of SM, also estimates the recurrence rate of SM at 14.8%, and suggests that altered sleep is a risk factor for recurrence.

“This study enhances our knowledge of and draws attention to a highly neglected but critically important topic. The fact that, in 2022, we know so little about status migrainosus is frankly shocking, particularly when we compare the volume of research on complications of epilepsy or stroke (e.g., status epilepticus, stroke recurrence risk) to that on the complications of migraine,” wrote Serena Orr, University of Calgary, Canada, in an accompanying editorial.

Orr continued, “Though patients may not die of status migrainosus, it is an incredibly disabling complication of migraine with widespread public health implications including loss of productivity and high healthcare-related costs. We sincerely hope that this work inspires our community to increase the focus on status migrainosus research such that we can provide better care to our patients down the road and reduce the burden associated with this disabling migraine complication.”

The new research and editorial appeared September 29, 2022, in the journal Neurology.

A database suited to the purpose
The sparseness of epidemiological information about SM, particularly in the general population, was the spur for the new work, according to VanderPluym.

“As someone who sees patients with migraine, we see certain complications of this condition that are extremely disabling to patients but that we actually have very little information about. There’s this huge gap in our knowledge, and so we wanted to do a study to better understand what status migrainosus is like out in the community, in a general population setting,” VanderPluym said.

To learn more, VanderPluym and her colleagues turned to the Rochester Epidemiology Project, a database with decades of medical services billing data for people living in Olmsted County. The nature of this database made it an excellent source of information to uncover the epidemiology of SM.

“It’s a very unique opportunity to have access to basically all the records for an isolated population. The residents of this community receive all of their medical services through a limited number of health facilities, and because of that, we have access to all of the diagnoses, hospitalizations, birth and death certificates – all that kind of information. This allows you to review a population’s lifetime of illnesses, which is ideal for trying to determine incidence,” said VanderPluym.

The researchers would go on to identify 237 cases of incident SM that met the criteria for the condition as specified by the third edition of the International Classification of Headache Disorders. An incident case was defined as the first physician-encountered case in the record, and cases would be followed for a year after the incident case. The study population had a median age of 35, and the majority had episodic migraine and migraine without aura, as well as a family history of migraine.

The tip of the iceberg?
After adjustment for age and sex, the incidence rate of SM was 26.6 per 100,000 person-years. The peak incidence occurred between the ages of 40 and 49. Further, when adjusted for age, the results showed that females had a higher incidence rate than males (46.97 vs. 6.23 per 100,000 person-years).

In the accompanying editorial, Orr wrote that the study’s incidence estimate of SM is “only the tip of the iceberg,” considering the homogeneity of the study sample, which was mostly white and female, and the barriers to accessing care that limit sample diversity. Meanwhile, VanderPluym said that because patients included in the study were only those who actually sought healthcare for their SM, “we view our incidence as probably the lower limit of what the incidence actually is.”

Another important finding from the study was that SM could last up to almost 10 days. VanderPluym said this was a particularly important result, since the upper limit of duration for an SM attack was previously unknown.

Further, for approximately 15% of the incident cases, there was a recurrence of SM, at a median of roughly two months after the first attack. In addition, more individuals had chronic migraine within a year from the incident SM, compared to at the time of the incident episode (roughly 48% vs. 36%, respectively), and more people whose episodic migraine turned into chronic migraine had a recurrence of SM within a year, compared to those who continued to have the episodic variety. These results piqued VanderPluym’s interest.

“When we looked at the timing of recurrence, it seemed like that occurred most commonly in that two-month window after the initial event, and two months is often the amount of time that we counsel patients it takes for preventive treatment to take action,” she said. “And so, this potential risk of chronification really begs the question: When we’re treating an episode of status migrainosus, do we not only need to consider an acute treatment in the moment to get relief, but do we also need to consider starting a preventive treatment, to potentially affect the recurrence of status migrainosus but also to potentially modify the risk of disease progression into a chronic migraine phenotype?”

Interestingly, though most subjects did not self-report triggers of their SM, alterations in sleep – too much or too little – were a predictor of recurrence, conferring an almost threefold increased likelihood of recurrence, compared to those without this trigger. VanderPluym said that sleep studies using techniques like actigraphy, rather than relying on self-report as the current study did, are needed to confirm this finding. But, she added that it’s encouraging, from a clinical perspective, that sleep may be a trigger for SM, considering that sleep is modifiable.

Some worrying findings
With regard to treatment, the study reported a few concerning findings. For instance, one in five patients had an opioid analgesic listed at the time of presentation of their SM. That is a problem since opioids are not a recommended treatment for migraine.

In addition, 19% of individuals in the emergency room/inpatient setting received an opioid prescription. “Unfortunately, it’s not surprising, but it is definitely concerning,” VanderPluym said, noting that other database studies have shown that opioids are being prescribed for migraine even though evidence does not support the use of these drugs.

One caveat is that the study did not ascertain why people were receiving opioids. It could be because other drugs were contraindicated or didn’t work, or because there was a lack of knowledge of best practices amongst healthcare providers seeing SM patients, VanderPluym cautioned.

The study also reported that 10% of individuals did not receive a documented treatment for SM, a finding that VanderPluym said was “extremely concerning,” particularly considering the increased risk of suicide in this patient group, compared to those without SM.

The present and the future
What are the immediate clinical implications of the findings? VanderPluym said that in her own practice, she is aiming to get in touch with her colleagues in the emergency department and in primary care to help disseminate knowledge about the management of SM. “We don’t have guidelines or a gold standard here, but we do have best-evidence recommendations.”

Based on the findings about SM possibly leading to chronic migraine, VanderPluym again emphasized that clinicians should consider preventive treatment and explore potential trigger factors.

In terms of follow-up studies, VanderPluym is working with the American Headache Society’s Refractory, Inpatient & Emergency Care Special Interest Section on large-scale literature reviews to determine if current diagnostic criteria for SM, as specified by the International Classification of Headache Disorders, are in line with what SM patients actually experience. Another review is assessing current treatments for SM.

VanderPluym also suggested that investigators do genetic studies of SM, to learn more about how patients with SM differ from those who don’t have this migraine complication. Pathophysiological studies of SM, “another huge gap in knowledge,” are also in order.

Neil Andrews is a science journalist and executive editor of the Migraine Science Collaborative. Follow him on Twitter @NeilAndrews

References
Incidence of status migrainosus in Olmsted County, Minnesota, United States: Characterization and predictors of recurrence.
VanderPluym et al.
Neurology. 2022 Sep 29. Online ahead of print.

Status migrainosus: One of the most poorly understood but important complications of migraine.
Orr SL.
Neurology. 2022 Sep 29. Online ahead of print.