Hundreds of thousands of Australians are needlessly enduring days of agony because they don’t know how to prevent migraines, researchers from The Australian National University (ANU) have found.
Once diagnosed migraines can be effectively managed.
But the researchers say sufferers don’t recognize the symptoms and so don’t seek the right treatment.
Dr Stephanie Goodhew, from the Research School of Psychology, says the study highlights a need for a public health campaign to inform the community on the treatments and defining features of migraines.
“Migraine is more than a headache.
It is an incredibly disabling condition that is also incredibly common – about 15 percent of the population suffer from migraines,” said Dr Goodhew.
“What is unique about it is that among neurological conditions, migraines are one of the most underdiagnosed or misdiagnosed conditions.
A lot of people have migraines and don’t realize they have it.”
“Even when people see their GP it can be missed or undiagnosed.
“People think having headaches is not big deal but having a migraine is not just a headache. It is a much more severe pain and can be debilitating.”
The study found one-in-five people who suffered migraine did not know about preventative medications they can access – which include Botox.
“This research shows people suffering from migraines often have incomplete or insufficient information about their own condition,” said Dr Goodhew.
“If we can allow people to have greater knowledge about migraine they can advocate for the right level of care.”
The study also showed one-in-five people who had migraine did not know about any of the dangers with acute medication treatments, which are often used to treat the condition.
“In the short term acute medications can massively reduce the pain but there are other risks if those medications are overused,” Dr Goodhew said.
The study found one-in-five people who suffered migraine did not know about preventative medications they can access – which include Botox. The image is in the public domain.
“They can create rebound headaches and they can create the problem that you are seeking to treat.”
“If you have migraines talk to your GP, arm yourself with knowledge and ask for a referral to a neurologist.”
Dr Goodhew says she struggled to find a diagnosis and appropriate treatment for her own migraines.
“I have had migraines my whole life, but I only received a diagnosis in my twenties,” she said.
“When I have one, looking at light induces a razor sharp pain and I was lucky enough to see a particularly savvy GP that realised I was light sensitive and referred me to a neurologist.”
The researcher says the challenge for practitioners is that there is no single biological marker that indicates someone is suffering from a migraine and people experience different symptoms.
“The source of the pain is often unilateral, on one side of the head whereas your standard headache is all over the head,” she said.
“Some people suffer from Aura – visual disturbances, or sensitivity to light. Others might feel nausea or dizzy.
Purpose
Premonitory symptoms (PSs) of migraine are those that precede pain in a migraine attack. Previous studies suggest that treatment during this phase may prevent the onset of pain; however, this approach requires that patients be able to recognize their PSs.
Our objectives were to evaluate patients’ actual ability to predict migraine attacks based on their PSs and analyze whether good predictors meet any characteristic profile.
Patients and methods
This prospective, observational study included patients with migraine with and without aura. Patients’ baseline characteristics were recorded. During a 2-month follow-up period, patients used a mobile application to record what they believed to be PSs and later to record the onset of pain, if this occurred. When a migraine attack ended, patients had to complete a form on the characteristics of the episode (including the presence of PSs not identified prior to the attack).
Results
Fifty patients were initially selected. A final total of 34 patients were analyzed, recording 229 attacks. Of whom, 158 (69%) were accompanied by PSs and were recorded prior to the pain onset in 63 (27.5%) cases.
A total of 67.6% of the patients were able to predict at least one attack, but only 35.3% were good predictors (>50% of attacks). There were only 11 cases in which a patient erroneously reported their PSs (positive predictive value: 85.1%). Good predictors were not differentiated by any specific clinical characteristic. However, a range of symptoms were particularly predictive; these included photophobia, drowsiness, yawning, increased thirst, and blurred vision.
Conclusion
A large majority of patients with migraine experienced a PS and were able to predict at least one attack.
Besides, only a small percentage of patients were considered as good predictors; however, they could not be characterized by any specific profile. Nonetheless, when patients with migraine believed that they were experiencing PSs, they were frequently correct.
When we talk about migraine attacks, we are generally referring to headache, which is usually the most disabling part of the attack.
However, migraine attacks encompass a far wider range of symptoms.
Prior to the pain, patients may experience the so-called premonitory symptoms (PSs), which were first described in 1980 by Blau1 and are defined as those symptoms that precede and alert patients of a migraine attack between hours and 2 days in advance. According to the International Classification of Headache Disorders, third edition (ICHD-3),2 they precede aura in migraine with aura and pain in migraine without aura.
Examples of PSs include euphoria, fatigue, depression, increased appetite, or cravings for a particular type of food.
Studying these symptoms is valuable as they are the first that patients report during an attack and can indicate which anatomical regions and neurochemical mechanisms are affected at onset (mainly, the hypothalamus, limbic system, and dopaminergic mechanisms).3,4
Another important factor, suggested in several papers, is the administration of the treatment during this phase with the aim of anticipating and preventing the pain onset.
Waelkens5 used domperidone as a treatment in response to the onset of PSs, while Luciani et al6 used naratriptan.
These studies reached similar conclusions, both using samples of ~20 patients. Pain was entirely prevented in approximately two-thirds of the patients; in the remaining one-third, pain occurred but was less intense. However, it should be noted that these studies included only patients who had previously been determined to be good predictors based on their PSs.
A large majority of studies about PSs in the literature followed a retrospective approach;7–13 it is not possible with this design to assess patients’ ability to predict attacks,14 which is fundamental if we intend to administer treatment during this phase.
The few prospective studies that do exist15–19 are mainly descriptive, with the exception of the articles by Giffin et al15 and Houtveen and Sorbi,19 which used electronic diaries to evaluate patients’ ability to predict migraine attacks.
The advantage of using these diaries is that data can be collected in real time, increasing prediction reliability. In these studies, patients completed a daily questionnaire with questions about “non-headache” symptoms. In the study of Giffin et al,15 there was also the possibility for patients to record symptoms spontaneously; however, the patients included in this study were selected due to their ability to predict migraine attacks.
As opposed to the methodology of Giffin et al and Hout-veen and Sorbi,15,19 our research does not ask the patients about their symptoms (reactively), but it allows them to spontaneously register their symptoms as soon as they appear (proactively), providing a set of potential symptoms to select from. Our aim is hence to exploit the capability of the patients to recognize their own symptoms in order to drive a potential early intake of the drugs.
Therefore, this study, besides using the benefits of electronic diaries through a mobile application, is the first to assess only the symptoms recognized spontaneously by patients not selected based on their ability to predict an attack and to proactively request the patients to register their PSs.
The study aimed to address the following questions: What percentage of patients are able to predict migraine attacks? Do they predict all attacks? Do good predictors have a specific profile? Is any combination of PSs particularly predictive?
Discussion
This study is the first to assess the ability to predict a migraine attack based only on spontaneous recordings made by patients when they experience what they believe to be a PS. This is of great importance for treating migraine during the premonitory phase:5,6 experiencing PSs is not the same as being able to recognize them as the onset of a migraine attack prior to the onset of pain.
Based on our findings, we can conclude that there is a high likelihood (67.6%) of patients being able to predict at least one migraine attack, but only one-third of our patients were good predictors (able to predict more than half of attacks).
Furthermore, only 27.5% of migraine crisis presents PSs a priori. However, it should be noted that patients who believed that they were experiencing a PS were very frequently correct (PPV was 85.1%).
No baseline variables were correlated with patients’ likelihood of being good predictors or of being able to predict any attack.
It is the case, however, that patients were more likely to recognize PSs if they considered the event to have been precipitated by a trigger factor, probably because they knew they would experience PSs. As one limitation of our study, we did not register the time of the trigger, so we cannot correlate them in time with the PSs.
Previous studies in the literature report conflicting results with regard to the prevalence of PSs in patients with migraine. Depending on the study, the reported prevalence ranges from 9%25 or 33%–39%8,9,11 to 77%–92%.7,10,13,16,26
This variability may be due to methodological differences between the different studies, for example whether the approach was prospective or retrospective (where a recall bias may exist, given that patients may not recall all PSs they experienced and the difficulty of associating PSs independently to each attack). Another influence may be the method of data collection: with free-form diaries, patients may forget certain items, whereas with checklists, they are limited to the available options or may record symptoms that they would not otherwise have reported or may have forgotten.14
We report one of the highest prevalence rates (85.3%). This may be due to our methodology: patients were able to add PSs that were not included on the provided checklist. A further detail that we deem relevant is the fact that time was specifically dedicated at the baseline consultation to performing a directed medical history interview and educating patients about PSs. Time constraints do not allow this at normal consultations. Therefore, patients often do not associate PSs with pain, as shown by the results of the survey, in which 47% of patients reported that they either had not recognized these symptoms or had not related them with migraine prior to the baseline interview. This argument supports the need of targeting the patients in a direct manner, as previously described in Jay and Barkin.27
We observed a mean of 4 PSs per event in our sample, whereas our literature review found that other researchers typically reported 3 PSs;10,13 this contrast was probably also due to differences in the method of data collection. Other articles described events accompanied by seven or even 12 of these symptoms.11,16 We also observed that the mean number of PSs reported per attack was lower for PSs reported prior to pain onset. This was probably because not all PSs are easily identified; predictive patients are more selective in recording PSs.
Various articles9–13,15–17,28 described yawning, irritability, apathy, neck stiffness, photophobia, nausea, fatigue, and difficulty concentrating as the most frequent symptoms. In addition to these, we also found perceived changes in body temperature and increased thirst to be frequent PSs.
Although the ICHD-3 beta29 definition stated that PSs may appear between 2 and 48 hours prior to pain, we found examples of PSs occurring later than 2 hours prior to pain onset. This issue has previously been discussed by Maniyar et al30
These authors considered that the definition involved two aspects that required consideration: first, PSs do not precede or forewarn of migraine attacks; rather, they are a part of the attack itself. Second, these symptoms may present during the 2-hour interval before the onset of pain/aura.
The reason for this time interval is to enable PSs to be clearly differentiated from aura; however, this gap does not truly exist, as has been shown by various prospective studies15,31 and now by the present study, with patients describing non-headache symptoms even minutes before pain onset. A
dditionally, aura is clearly a distinct entity from a pathophysiological perspective. In the definitive version,2 the specification of 2 hours has already disappeared and the PSs are considered possible part of the migraine attack.
In our sample, PSs occurred a mean time of 10 hours prior to pain onset; this is consistent with previous studies, which describe a mean time of 6–12 hours.15,19 As other authors have found to be the case,19 certain symptoms were typically observed to occur closer to pain onset (neck stiffness, nausea, apathy, difficulty concentrating, and fatigue), while others occurred earlier (perceived changes in body temperature, anxiety, osmophobia, yawning, allodynia, and tinnitus).
Such authors as Waelkens26 also describe these early symptoms. Other early PSs described in the literature include mood alterations such as euphoria and hyperactivity;26 however, our results do not support this conclusion, as very few of the patients in our sample recognized these PSs; Giffin et al15 reported similar findings.
This variability in the time of onset of PSs is supported by neuroimaging studies, which reveal different brain activation patterns depending on the phase of the migraine. Maniyar et al32 artificially induced migraine in patients and observed activations in specific areas at onset of the migraine attack, in accordance with the PSs reported by the patient. It should be noted that activation was different during the early and late premonitory phase.
The activation of areas including the hypothalamus, ventral tegmentum, peri-aqueductal gray, and putamen diminished nearer pain onset; the dorsal pons remained active in all phases, and the insula was activated nearer the time of pain onset. This is probably linked to the fact that certain PSs occur at the earliest moment of the premonitory phase, maintaining a constant intensity, and disappear before pain onset (non-evolutive symptoms), whereas others increase in intensity approaching pain onset (evolutive symptoms).4,26
As was mentioned earlier, the main study into patients’ ability to predict pain in migraine attacks based on their PSs was conducted in 2003 by Giffin et al.15
In this study, patients were required to record the different cognitive, sensory, and mood alterations they experienced, as well as any other symptoms. The researchers then analyzed whether symptoms changed in the days and hours before pain onset. Patients considered good predictors (n=97) were able to predict 72% of attacks; 82% of patients predicted more than half of their attacks.
This stands in contrast with our findings (35% of our patients predicted more than half of their attacks), which can be explained by two facts. First, we included in our study any migraine patient and not only those considered as “good predictors”, because the aim of our work was to evaluate the prediction capability of all our patients visiting for migraine diagnosis.
Additionally, in the work of Giffin et al, it is related how the patients were instructed to fill a form upon a daily alarm, although spontaneous registers were also allowed. In that work, we can observe that most of the valid data (68%) were obtained right after the alarm. However, if we aim to advance the intake of the treatment before the pain starts, the patients must recognize these PSs. Therefore, we only allowed patients to register data spontaneously.
The most predictive PSs in the study of Giffin et al15 were difficulty speaking, difficulty reading and writing, and yawning; these symptoms were also frequently recorded prior to pain onset in our study. In our study, the most relevant PSs (considering the number of times each PS was recorded, its predictiveness, and its PPV) were photophobia and drowsiness.
These symptoms were also found to be predictive in the study of Giffin et al; other very relevant symptoms to be taken into account, based on the evaluation of both studies, are blurred vision, thirst, dizziness, perceived changes in body temperature (especially high temperature), food craving, and difficulty concentrating. Other symptoms did not aid patients in predicting attacks; examples are sadness and apathy.
Regarding nausea and vomiting, the results of the two studies diverge: the present study found this to be a good predictor, while this was not in the case of the study of Giffin et al. As can be seen in the study of Giffin et al, although nausea and vomiting are registered a priori in many of the events, there is also a large percentage of prediction error related to these PSs. However, our study found that the PPV of these symptoms is 80.
Another interesting point is that the machine learning techniques used enabled us to tell patients with a precision of almost 80% whether their attacks may be predictable, based on the PSs they reported.
After reviewing the patient surveys, we observed that patients know whether they were able to predict some migraines, but were often mistaken regarding their self-identification as good predictors. We deem it important to verify this information as patients may under- or overestimate their ability to predict attacks.
The main limitations of this study are as follows:
1) the small sample size;
2) the fact that using a mobile application excludes those patients who do not have basic user-level understanding of smartphone-type devices, who often are aged patients;
3) the exclusion of patients who consistently recorded symptoms incorrectly; and
4) the fact that probably patients were more focused on recognizing their PSs than usual due to the 2-month study period.
These limitations probably result in an overestimation in predictability. Despite this, we consider the study’s strengths to be its real-time approach, the ability to study multiple migraines and baseline characteristics, and the machine learning analysis. In conjunction with the large amount of data and the application installed on patients’ own telephones, this has afforded great reliability to the study’s reflection of patients’ everyday condition.
Conclusions
With appropriate training, a large majority of the patients in our study successfully identified their PSs and were able to predict at least one attack.
However, a strategy of administering treatment during the premonitory phase, based only on prior recognition of symptoms, would benefit a very small percentage of patients.
We found no baseline characteristic offering insight into a patient’s status as a good predictor; analyzing the PSs itself was found to be more informative.
Nonetheless, it should be stressed that patients who believed that they were experiencing a PS were correct in a large majority of cases; this effect was more pronounced for specific symptoms. We deem it fundamental for the future treatment of migraine attacks for researchers to continue to seek the best method of predicting pain onset.
Source:
Australian National University
Media Contacts:
Press Office – Australian National University
Image Source:
The image is in the public domain.
Original Research: Open access
“Migraine Literacy and Treatment in a University Sample”. Stephanie C. Goodhew.
Springer Nature Comprehensive Clinical Medicine doi:10.1007/s42399-019-00124-y.
