A recent phase 2 study was undertaken to investigate the safety and efficacy of a monoclonal antibody (Lu AGO9222) to pituitary adenylate cyclase-activating polypeptide (PACAP) for prevention of migraine. PACAP is a widely distributed vasodilating polypeptide, it binds to receptors in areas of the central and peripheral nervous system known to be important in the pathophysiology of migraine.

Trial participants had a substantial headache burden with a mean of 16.7 migraine days per month documented during a 4 week run in period. 2-4 previous preventative treatments had failed to provide a benefit. An infusion of the antibody, given over a period of 30 minutes, reduced the number of monthly migraine days by 6.2 days, as compared to a reduction of 4.2 days in the placebo group. Adverse events were described as mild and included nasopharyngitis and fatigue. Whilst 2 fewer days a month may be less than what was hoped, this does add up over a year to a benefit of almost one month of migraine free days from the medication.

It is always good news to have another potential treatment option for migraine. Not all patients respond to the currently available therapies, and this probably reflects the diversity of the underlying causes of migraine. This trial offers hope that future options may be of benefit to patients who are yet to find a positive response to currently available treatments.

Further trials will evaluate subcutaneous formations of the PACAP antibody, and we await their outcome with great interest.

Reference: Ashina M et al, A Monoclonal Antibody to PACAP for Migraine Prevention, N Engl J Med 2024; 391(9):855-857

Severe acute respiratory syndrome coronavirus 2 (SARS-C0V-2) is a novel coronavirus, responsible for the coronavirus disease (COVID 19) that emerged in China at the end of 2019 causing the current global pandemic. In our Headache clinic we have seen a number of referrals of ongoing headaches and migraines post COVID infection. A similar observation has been noted by Headache and Migraine clinics around the world and this was explored further in a recent case series published in the American Headache Society’s, Headache the Journal of Head and Face Pain (May 2021)

In this blog we will summarise these 3 cases, and similar presentations have been observed in our patient cohort.

Patient 1: Migraine Chronification
A 56 year old woman with a history of low frequency migraine reported a mild COVID 19 infection associated with symptoms of headache, lack of smell, and malaise. Headache was the first symptom of the infection, starting a couple of days prior to the other symptoms. She reported it was different from her usual migraine in that the pain since onset was constant. The relentless nature of the pain was associated with the patient starting to overuse acute medication. In addition the patient started to notice tenderness (allodynia) while combing her hair. At the headache clinic she complained additionally of fatigue and insomnia. Given the combined headache and sleep disturbance complaint Amitriptyline was commenced. This resulted in improved sleep quality, however she continued to experience almost daily headaches. OnabotulinumtoxinA was added to her treatment regimen, with a reduction in headache frequency and a return in character to her usual migraine.  

Patient 2: Long Lasting COVID Headache
A 55 year old woman with no personal or family history of migraine experienced a mild case of COVID 19 infection. Her initial symptoms were that of loss of smell and taste, cough, shortness of breath, feeling systemically unwell, and diarrhoea. A persistent headache started a few days after the appearance of her other symptoms. She presented to the clinic with this ongoing headache as well as with symptoms of fatigue, and insomnia. Combination treatment was commenced with amitriptyline and onabotulinumtoxinA. After 3 months of treatment she reported improved sleep quality and her headache severity and frequency was reduced by 50-75%. Ongoing symptom control was reported over subsequent treatment cycles.

Patient 3: Delayed onset COVID Headache
A 44 year old man with no history of migraine had a mild COVID 19 infection associated with cough, shortness of breath and malaise. As his respiratory symptoms began to improve after 2 months, he started to report daily, constant headaches, at times the events were associated with migrainous features of throbbing pain, sensitivity to light and sound, nausea, and worsening of pain with movement. On his presentation to the headache clinic he complained additionally of fatigue and insomnia, and his blood pressure was found to be elevated at 140/90. He was commenced on Amitriptylline for his poor sleep, and Candesartan for his high blood pressure. On the follow up visit his blood pressure was controlled, and sleep quality had partially improved, though no changes to his headaches were reported. Subsequently OnabotulinumtoxinA was added, as well as Rizatriptan for acute events, however these were not effective. On his most recent visit changes in mood and memory were reported with antidepressant therapy commenced, he reported continuing to experience disabling, daily, and constant headache, and had not returned to work or his usual activities.

These cases are instructive, and we have seen cases similar within our own Headache clinic. Patient 1 suggests that COVID 19 is a risk factor in the worsening of an underlying headache disorder, in this case, triggering the development of chronic migraine. Patients 2 and 3 were without a personal migraine history, though infection with COVID seems to have been associated with the development of migraine like features, suggesting acquired activation of the trigeminovascular system by the infection. In patient 3 persistent headaches emerged despite not having experienced headache in the acute infection phase. Case 3 in particular was noted for Headache in association with other symptoms (insomnia, memory loss, dizziness, fatigue), that may identify as ‘post COVID 19 syndrome’. The presence of these co-morbid conditions could point to the involvement of different pathophysiological pathways , such as the brainstem and neurotransmitter depletion in neuropsychiatric symptoms.

Treatments for post COVID Headache
Many patients with a history of migraine report that the headaches associated with COVID are different, either more severe, or long lasting. At this stage it is too early to recommend treatments for headache associated with COVID. In general however, when patients describe migraine like headache after COVID infection, migraine therapies are recommended, and patient 1 and 2 reported improvement following OnabotulinumtoxinA. In addition, if other symptoms are reported such as poor sleep, then medications that address these issues, as well as migraines, can be chosen.

References:
Toward a better understanding of persistent headache after mild COVID 19: Three migraine like yet ;distinct scenarios; Edoardo Caronna, MD,  Alicia Alpuente MD, Marta Torres-Ferrus MD, and Patricia Pozo-Rosich MD, Headache 2021 Sep; 61(8): 1277–1280.

Migraine and Post COVID Headache; American Headache Foundation, Published; February 17, 2022

Migraine headaches often improve during pregnancy, but have also been known to exacerbate, or even commence during this time. Encouragingly almost half of women with migraine have improvement during the first trimester, and this improvement increases significantly in the second (83%) and third (87%) trimesters.

It is important to develop a plan for preconception counselling and migraine treatment during pregnancy. During the preconception visit, plans to discontinue preventative medication prior to conception are discussed. Removal of the migraine preventative may result in increased migraine events, and patients are encouraged to consult additionally with an obstetrician to address any fertility concerns. In addition, it is advised to engage in lifestyle modifications including sleep hygiene, exercise, such as yoga, as well as therapies including biofeedback and acupuncture.

For migraine headache events first line treatment is acetaminophen, in addition caffeine and metoclopramide are advised. Failing this, Sumitriptan is the most studied and preferred choice of triptan during this time. Insufficient data currently exists for the other triptan medications to recommend these alternatives.

If preventative medication needs to be started during pregnancy, severity of disease is considered, with a risk/benefit, and case by case analysis considered. For women with significant disability due to migraine, the risk of medication needs to be weighed against the health consequences of untreated migraine, which can negatively affect the mother and the foetus. Untreated migraines can lead to reduced oral intake, resulting in poor nutrition and dehydration, in addition to lack of sleep, increased stress and risk of depression.

In the first trimester, Greater Occipital Nerve Blocks (GONBs) are the preferred treatment. Second line options include propranolol or amitriptyline. Topiramate (increased risk of cleft palate) and Valproate (known to be associated with neural tube defects and neurodevelopmental disorders), are not safe during pregnancy.

For patients with chronic migraine, who do not respond to GONBs, with significant disability, and who had improvement with OnabotulinumtoxinA prior to pregnancy, recommencement on this therapy is considered. This is supported by a recent retrospective review of 232 women with exposure to OnabotulinumtoxinA 3 months before, or during pregnancy, which did not show an increased risk of foetal abnormalities.

Neuromodulation devices can also be considered, and although specific evaluations of these devices in pregnant women is lacking, encouragingly no foetal malformations or birth defects have been observed.

We often get asked about Calcitonin gene related peptide (CGRP) blocking monoclonal antibodies, recently approved for migraine prevention. These drugs were not however tested during pregnancy. CGRP does have a role in pregnancy vasculature, and the medications are to be avoided during pregnancy until further studies are performed. Given this, it is important, given the long half life with these agents, to discontinue the preparations at least 5 months prior to conception.

Reference:
Practical Neurology; Kate Onorato MD, Carrie Dougherty MD FAHS, Jessica Ailani MD, FAHS; May 2019

A new anti-calcitonin gene related peptide antibody therapy has shown efficacy in the preventative treatment of chronic migraine. The medication is distinctive compared to other CGRP antibody therapy in that it is administered by intravenous infusion, and reaches maximum plasma concentration in about 30 minutes, corresponding to the end of the infusion.

The medication is also unique in that a recent study indicates that this infusion therapy may provide benefits within hours of the infusion, with more frequently resolved acute migraine pain compared to placebo.

Patients with migraine have previously had to wait several weeks for the effect of their preventative medications to manifest, often resulting in extended periods of pain and reduced functioning, with potential visits to emergency departments to obtain migraine relief, and risk of overuse of acute medication.

Treatment with the iv infusion more frequently resolved headache pain at 2 hours compared to placebo. Additional studies have shown the magnitude of the benefit observed at day 1 was sustained over the 12 week dosing interval.

The data would suggest therefore that the new intravenous therapy has the potential to address both the acute and preventative treatment needs of patients with migraine. It raised the potential of being both an effective treatment preventing future attacks of migraine, with the added benefit of alleviating an acute migraine attack.

References:

Winner PK, McAlister P, Chakhava G et al Effects of Intravenous Eptinezumab vs Placebo on Headache Pain and most Bothersome Symptom when initiated during a Migraine attack A Randomised clinical trial, JAMA 2021, 325 (23) 2348-2356

Lipton RB, Goadsby PJ, Smith J et al, Efficacy and safety of Eptinezumab in patients with chronic migraine PROMISE-2, Neurology 2020;94:e1365-e1377

CGRP monoclonal antibody therapies are a new preventative treatment option for migraine. There are currently no existing treatments that eliminate migraine entirely, though these drugs have been shown in clinical trials to reduce migraine event frequency and severity in a moderate number of patients who experience frequent, disabling attacks. These medications are generally well tolerated, and are self injected on a regular schedule (monthly).

You should consider CGRP monoclonal therapy if you:

• are moderately to severely disabled by frequent migraine attacks
• have not benefited from existing treatments
• have difficulty tolerating existing migraine treatments

You should avoid these drugs if you:

• experience infrequent migraines and respond well to your existing treatment
• have cardiovascular disease, or are at high risk of heart disease or stroke
• are pregnant or trying to become pregnant
• suffer from severe constipation

Other issues to consider with CGRP monoclonal antibody therapy

The long term safety risks of this class of medication are still unknown.  If you are tolerating existing treatments and are satisfied with your control of migraines, this uncertainty needs to be kept in mind. In addition, patients with psychiatric or complex medical conditions were excluded from clinical trials, and it may not be appropriate to generalize the findings to patients with these co-morbidities.

Migraine is a complex disorder, and as can be seen, multiple factors need to be taken into account before any new treatment is prescribed. If you would like to be considered for this class of medication a discussion with a headache specialist is therefore advised to review your individual treatment suitability.

–Dr Nicole Limberg

Do you suffer from mild or chronic migraines? If you’ve considered keeping a migraine diary (and we’d recommend you do) here’s why you should. Keeping a migraine diary helps you and your healthcare team to track the characteristics of your migraines and understand patterns and possible triggers. In fact, we recommend a migraine diary to all of our patients at Migraine Specialist in Brisbane.

The 6-8 hours prior to a migraine attack are the most important to track and retrace, as this can give you and your team of medical professionals valuable information to help diagnose, prevent and treat your migraines in the future. The more information you can provide your healthcare team, the better, so take an active role in your migraine prevention and management plan today and keep a migraine diary.

But don’t worry, it doesn’t have to be a long and arduous task – we’ve compiled some tips in this article to help you and we’ve put together a migraine diary template that you can print out and use at home.

Why should you keep a migraine diary?

A migraine diary is an important tool for your treatment team to use to help identify patterns and triggers and track the impact that medications have on your migraine symptoms and side effects.  A migraine diary also helps medical to chart your progress over time, understand what is working and what isn’t and assess when, how and why you are experiencing regular migraine attacks.

Without this information, your team of medical professionals will not be able to help you as effectively as they could, so it’s a really important part of your ongoing migraine treatment plan.

What you should include in a migraine diary?

Your migraine diary should answer the following questions…  

• Did you experience a headache or a migraine?
• What was the severity of the pain on a scale of 0-10?
• Where was the pain located?
• What symptoms did you experience during the migraine attack?
• What day of the week and at what time did you experience the attack?
• What was the duration of the attack (hours and/or days)?
• What did you do before the migraine attack and what could be a possible trigger?
• What medications did you take during the migraine attack (including prescription and non-prescription)?
• What did you do to relieve the symptoms and pain during the migraine attack? Did it work?
• How much sleep did you have the night before the migraine attack?
• What is the weather like?

In addition, women should record their menstrual days in their migraine diary to assess whether this has any impact or influence on migraine onset. There are some great articles already on the Migraine Specialist blog about menstrual migraines, menopause and migraines and migraines in women that are particularly helpful to women who suffer from regular migraines.

Here is an example of a completed migraine diary entry.

An active lifestyle and nutritious diet are important for your overall health, but did you know research suggests there is a link between nutrition and migraines specifically? From dietary changes that help prevent migraines to tips on what to eat and drink when you are experiencing a migraine, in this article, we explore the link between nutrition and migraines.

While certain foods or chemicals may trigger a migraine in one person but not another, there are some common dietary triggers for headaches and migraines. These include:

• Chocolate
• Processed meat
• Citrus fruits
• Cultured dairy products
• Aged cheese
• Caffeine – in coffee, energy drinks and tea
• Foods that contain additives like monosodium glutamate (MSG), nitrates and aspartame
• Some wines, beers and spirits

In addition to these food triggers, dehydration and your dietary eating habits and patterns, such as missed, delayed or inadequate meals, can trigger migraines too.

So, what changes can you make to your diet to prevent headaches and migraines or help relieve them during an attack?

Understand what your dietary triggers are

The first step is to work out what your dietary headache or migraine triggers are. You can do this by keeping a headache food diary, recording what you ate and any headache/migraine symptoms that occur as a result. Look for patterns and foods that trigger your headaches and then avoid these foods and find alternatives to them. This may involve spending some time reading food labels and eating more home cooked meals so you are aware of exactly what you are eating.

Once you know what your dietary triggers are, it is much easier to avoid and prevent them by planning your meals in advance and making better options when eating out.

At Migraine Specialist, we ask all of our patients to carefully complete headache diaries as part of their treatment plan, and detailing the food they eat and the symptoms they experience is an important part of that.

Small changes that will have an impact

In addition to learning more about what your personal dietary triggers are, you can also make some general changes and substitutes to help with prevention and management of your migraines. These small changes include:

1. Eat more fresh foods such as vegetables, fruit, whole grains and lean proteins and avoid foods with added preservatives like MSG.
2. Stay hydrated – Avoid dehydration by drinking a minimum of 2-3 litres of water throughout the day. Of course, this will depend on your climate and activity level, but make sure you are getting at least 2-3 litres each day. A good way to keep track of your water intake is to carry a water bottle around with you and make sure you drink a lot of water especially if you feel a headache or migraine coming on.
3. Keep your blood sugars stable and eat regular meals and snacks that are balanced. Choose fibre rich, wholegrain or low GI carbohydrate foods and avoid missing or delaying meals.
4. Include probiotic and prebiotic foods in your diet for your gut. Probiotic foods include sauerkraut, miso, kombucha, tempeh and kimchi and prebiotic foods include oats, asparagus, garlic and legumes.

The relationship between your gut and brain

We spoke to nutritionist Dietitian & Nutritionist Rebecca Gawthorne about the connection between your gut and brain, and how this can impact headaches and migraines.

Rebecca said, “Your gut and brain are closely connected and research is finding that maintaining a healthy gut may benefit headache and migraine sufferers. Research suggests that those who regularly experience gastrointestinal symptoms have a higher prevalence of headaches than those who don’t have gastrointestinal symptoms, meaning that those who get frequent headaches may be predisposed to gastrointestinal problems. Digestive conditions, such as irritable bowel syndrome and celiac disease, also may be linked to migraines. Treating these digestive conditions may help reduce the frequency and severity of migraines.”

Rebecca also said when you include probiotic and prebiotic foods in your diet, you can help your gut maintain a healthy balance of gut bacteria and which in turn, may reduce headaches and migraines.

What should I eat during a migraine

We know that migraines are uncomfortable, painful and debilitating, and there are lots of side effects. While it is important to follow advice from your doctor or medical professional and take prescribed medications during a migraine attack, both Rebecca and Dr Limberg have also offered nutritional and diet suggestions that may be helpful when you are experiencing a headache or migraine.

Firstly, if you feel a headache or migraine coming on or are experiencing an attack, drink lots of water and stay hydrated to relieve the pain. If you are experiencing nausea, you may need to sip slowly on water and if you have been vomiting, an electrolyte replacement drink can help rehydrate you more effectively.

If you feel like eating, bland folds like plain crackers or bread can also help if you have been vomiting. Some people may also find ginger or peppermint helpful in relieving symptoms.

In addition, avoid any of your headache and migraine trigger foods and opt for foods that you know don’t cause any migraine symptoms for you, such as fresh vegetables and fruit. If you think that your headaches and migraines may be related to skipping a meal, eating something containing carbohydrates, like some fresh fruit, may help.

Dr Limberg also said that caffeine can have pain relieving effects, and a cup of coffee, with a combination of analgesic medications, can be beneficial at the onset of a migraine event.

Most importantly, know that you don’t have to suffer alone and in silence – there are so many options for prevention and management no matter how minor or severe your headaches and migraines are. Check out our blog for more resources on headache and migraine prevention and management, or give us a call on (07 3831 1611) if you want to chat to our team about a solution that is right for you.

If you know someone who suffers from frequent headaches and migraines, pass on this article so they can make some small diet and nutritional changes that have a big impact.

Thanks to Dietitian & Nutritionist Rebecca Gawthorne and our Neurologist Dr Nicole Limberg for their advice and expertise on the link between nutrition and migraines for this article.

The use of cannabis or marijuana, for medicinal purposes is deeply rooted through history, dating back to ancient times. It once held a prominent position in the history of medicine. The father of modern medicine, Sir William Osler, published the textbook, ‘The Principles and Practice of Medicine’

School holidays are upon us and many of you may have taken the kids along to see Incredibles 2.  The movie has a warning for “photosensitive conditions’, migraine is one of these, today we discuss photosensitivity in this condition, as well as other sensory triggers in our blog.

Migraine is associated with altered processing of sensory stimuli.

Migraine attacks typically consist of intense, unilateral, throbbing headaches that are associated with sensitivities to light, sound, odours, and stimulation of the skin, as well as nausea and vomiting with or without accompanying auras.

Several studies have demonstrated that migraines differ in their processing and perception of sensory inputs. During the migraine attack, migraines develop an enhanced perception of painful and non-painful sensory, visual, auditory, and olfactory sensations.  Between migraine attacks, atypical sensory perception persists, with migraines often demonstrating low discomfort thresholds to various experimentally applied stimuli.

Migraineurs have hypersensitivity to auditory still, altered perception of sound, an abnormal acuteness of hearing, activation of migraine attacks with auditory triggers and aversion of noise during migraine attacks. Approximately two=thirds of migraines report sensitivity to sound between migraine attacks.  Migraineurs report that noise, such as traffic noise, can trigger migraine attacks.  Sensitivity to sound increases during a migraine attack.  Approximately 70-90% of migraine patients report sensitivity to or aversion to noise during a migraine attack.

Various odours, including pungent odours, perfumes, food smells, cigarette smoke and cleaning detergents, can be irritating to migraines. Migraineurs report sensitivity to odours during and between migraine attacks.  Between attacks, migraines can detect the odour of vanillin, a pure olfactory nerve stimulant, at weaker concentrations compared with non-migraine healthy controls.  About 50% of migraines report that odours can trigger their migraine attacks.

Migraineurs process and perceive visual information atypically. Most migraines report increased sensitivity to light between migraine attacks (75%) and light-induced aggravation of headache during a migraine attack (60-90%).  As with auditory stimuli, migraine’s have reduced visual discomfort thresholds as compared to non-migraineur.  Various visual stimuli can trigger a migraine attack, including exposure to sunlight, flashing or flickering lights, television, computer screens, and patterned lights.

Enhanced perceptions of sensory stimuli that are normally painful as well as those that are normally non harmful are displayed by Migraineurs. Approximately 60-70% of migraines develop cutaneous allodynia during the migraine attack. That is, they describe normally non harmful stimulation of the skin as painful.  For allodynic migraineurs, shaving, showering, wearing earrings and classes and brushing hair can cause pain.

Migraineurs differ from non-migraineur in their processing of sensory stimuli. Increased sensitivity to sensory stimuli, lower discomfort thresholds to such stimuli, and migraine attack triggering via visual, auditory, and olfactory stimuli serve as evidence for atypical basal functioning of multiple regions in the migraine brain.

Future studies are needed to further define the mechanisms underlying atypical processing of sensory stimuli in migraineurs between and during migraine attacks.

Reference:

Curr pain Headache Rep. Harriott, Schwedt, 2014 Nov:18(11):458

Note: Information on this site is not a substitute for professional medical advice.

Migraine is one of the most common neurological disorders and it impacts women more than men at a rate of 3:1. It is well established that sex hormones play an important role in the epidemiology of migraine. As children, boys and girls are equally affected, but the female predominance emerges after puberty which is why migraines in women are much more common than in men.

Many women who suffer from migraines note an increase in attacks in the perimenstrual period. Compared with non-menstrual migraines, menstrual migraines cause more impairment, are longer and are more likely to relapse within 24 hours, which significantly increases their burden.

Gender also plays a role in the chronification of headache, likely due to hormonal differences, and women have a higher prevalence of chronic daily headache than men. In addition, several studies have suggested that women have more frequent, more severe and more long-lasting headaches when compared with men. Women also experience more of the associated symptoms of light and noise sensitivity and nausea.

Women, pregnancy and migraines

For some women, a worsening of their migraines may be the first indicator of pregnancy. Migraines worsen during pregnancy because of factors such as the hormonal changes of pregnancy, nausea, dehydration, lack of sleep and stress. However, 60 to 87% of women with menstrually related migraine (MRM) improve in the second and third trimesters.

To minimize risks to the developing fetus and reduce pain and disability in women during pregnancy, approaches to treatment that do not include medication are recommended. Instead, lifestyle factors such as a healthy diet and regular sleep, maintaining good hydration, minimizing caffeine intake, avoiding triggers, moderate exercise and acupuncture, icepacks or heat are some ways to prevent and manage migraines during pregnancy.

Migraine symptoms often become apparent in the postpartum period as oestrogen levels rapidly fall. Breastfeeding may delay the return of migraines because it keeps oestrogen levels elevated.

Women, menopause and migraines

For many women, the period prior to menopause brings worsening migraines because the combination of fluctuating ovarian function with fluctuating hormone levels results in irregular periods, hot flushes, sleeplessness and difficulty concentrating. This chaotic hormonal combination can lead to higher migraine frequency and worsening severity, even for women who have suffered from relatively mild or infrequent migraine attacks in the past.

There is more information about women, menopause and migraines in this article.

Migraine is one of the most common neurological conditions and is the third most common disabling disorder globally. Women are disproportionately affected by a ratio of 3:1, compared to men, in part due to hormonal differences, with changes in oestrogen appearing to be the principal factor.

If you’re suffering from regualr migraines and you’re unsure of the cause or need a personalised treatment plan, reach out to our team at Migraine Specialist.

Note: Information on this site is not a substitute for professional medical advice

References:

Migraine in Women, Broner MD et al, Semin Neurol 2017; 37:601-610