“This indicates a large unmet need to diagnose and treat migraine in GWI and CFS”

Could chronic fatigue syndrome be a form of migraine? That might not be so wacky an idea as it sounds. About ten years ago Puri and Chaudhuri suggested chronic fatigue syndrome was similar to migraine. In the last two years not only have Baraniuk’s studies indicated high rates of migraine are present in ME/CFS but other studies have found that many people with migraine meet the criteria for ME/CFS.

head exploding

Are similar central nervous system problems contributing to both migraine and chronic fatigue syndrome?

Finding similar incidences of migraine in Gulf War Syndrome and ME/CFS in their latest study, Baraniuk and Rayhan smushed the two together and then added fibromyalgia to the mix as they proposed GWI, ME/CFS, FM, and migraine are kind of like kissing cousins.

“Similar patterns of gray and white matter abnormalities and altered brain energetics in GWI, CFS, FM, and migraine suggest that common central mechanisms may contribute to the type of headaches and cognitive impairments perceived as ‘brain fog’. “

Let’s check out more of the migraine/ME/CFS connection.

The ME/CFS Migraine Connection

Besides symptoms and high rates of comorbidity, the relapsing-remitting nature of both disorders, the problems with barometric pressure changes, some similar triggers (including exercise for some), similar central nervous system abnormalities, etc. make a possible connection between migraine and ME/CFS/FM an intriguing one.

Consider that about three times as many women as men get migraines. Consider that both migraines and ME/CFS symptoms are often substantially reduced during pregnancy. Consider that central nervous system hyperactivity plays a role in both conditions, that both feature blood vessel problems and inflammation is a key factor in both.

Consider that stress often plays a key role in triggering both migraines and symptoms in ME/CFS. Consider that during migraines and relapses in ME/CFS exertion and exposure to stimuli often must be curtailed dramatically. Whether in the midst of an ME/CFS crash or migraine attack hypersensitivity to lights, sounds and odors is common.

Let’s see what their studies found.

The Studies

Migraine in gulf war illness and Chronic Fatigue Syndrome: prevalence, potential mechanisms, and evaluation Front Physiol. 2013 Jul 24;4:181. doi: 10.3389/fphys.2013.00181. Rayhan RURavindran MKBaraniuk JN.

Migraine headaches in Chronic Fatigue Syndrome (CFS): comparison of two prospective cross-sectional studies. Ravindran MK, Zheng Y, Timbol C, Merck SJ, Baraniuk JN. BMC Neurol. 2011 Mar 5;11:30. doi: 10.1186/1471-2377-11-30.

Baraniuk and Rayhan did ‘structured headache evaluations’ and tested for the evidence of widespread ‘hyperalgesia’ (increased sensitivity to pain) in 50 Gulf War Illness (GWI), 39 ME/CFS, and 45 controls in the 2013 study. The presence of hyperalgesia was tested by applying pressure to different areas of the body. A person was classified as having a migraine if they had had five or more episodes lasting 4-72 hours that included at least two of the following:

  • Unilateral headache (headache on one side of the head)
  • Pulsatile quality
  • Moderate-severe pain severity
  • Aggravation of the headache by doing usual activities
illustration of scotoma

A representation of a scotoma or zigzaggy line sometimes occurring in auras in migraines.

In addition, sensitivity to light or sound or nausea (with or without vomiting) was required.

(Many forms of migraine exist; abdominal migraines involve nausea but do not cause head pain; cluster headaches typically cause eye pain, eye-watering, and a stuffy nose. Aura’s can involve vision problems (zigzag lines, flashing lights, blind spots, eye pain, blurred vision), pins and needles sensations in an arm or leg, speech problems, and weakness. Aura’s typically precede headaches in about 20% of migraines and are not always followed by a headache. Other migraine symptoms can include increased sweating and urination, face swelling, and fatigue.)

The Results

High rates of migraine occurred in both ME/CFS and GWI groups. Migraines were present in 64% of GWI and an astonishing 82% of ME/CFS patients vs. 13% of the healthy controls. Fully two-thirds of the ME/CFS and GWI patients experienced auras (flickering lights, rotating discs, photosensitivity, loss of vision) with their migraines. That people experiencing auras also tended to experience more pain suggested that when things go wrong they really go wrong. Almost 70% of ME/CFS migraine sufferers also had tension headaches.

merging heads

Most people with ME/CFS had migraines and many migraine sufferers meet the criteria for ME/CFS

Low rates of tension headaches without migraine in ME/CFS (8%) patients and GWI patients (20%) suggested the two types of headaches usually occurred together. ME/CFS patients with just tension headaches had lower pain scores overall.

Except for lower rates of migraine with aura, the 2011 ME/CFS study found similar results.

As if migraine wasn’t enough, systemic hyperalgesia (increased and widespread pain sensitivity) was present in 62% of GWI and 70% of ME/CFS patients. With that kind of result, it wasn’t too surprising to find that over half of ME/CFS (56%) and 38% of the GWI participants meet the criteria for fibromyalgia.

That both ME/CFS and GWI patients with migraines had significantly lower systemic and sinus pain thresholds suggested to these Georgetown researchers that they were suffering from a ‘central sensitization’ disorder that increased their pain levels system-wide.

Systems Biology Approach Requested

Rayhan and Baraniuk called for a ‘fresh, systems biology’ approach in ME/CFS, GWI, FM, and migraine that integrated all the systems involved in filtering and assessing sensory data from the body. This would include systems such as the insular cortex where misinterpreted sensory data would perceived as a ‘serious illness’, and inflammation or other triggered glutamate releases that resulted in increased pain signals (hypersensitivity).

They proposed that dysregulated sensory inputs to the brainstem could cause many problems including high levels of pain, fear (PTSD), and reduced executive functioning (decision-making and planning, aka brain fog). They suggested, interestingly, that ion channelopathies–which we haven’t heard about for a while–that trigger widespread neurotransmitter release (e.g., glutamate?), may be present.  Basant and Puri proposed that a neurological channelopathy was present in ME/CFS about 10 years ago.

Migraine Model Proposed for Chronic Fatigue Syndrome

“It is tempting to speculate that the parallel findings of GWI, CFS and migraine indicate a shared underlying pathophysiological mechanism” Rayhan and Baraniuk, 2013

Noting that 67% of migraine sufferers meet the criteria for ME/CFS, they suggested that the cortical spreading depression (CSD) known to occur in migraine may provide a model for the central sensitization at work in ME/CFS and GWI.

Several processes can cause CSD but the most relevant for ME/CFS involve a) a wave of ischemia (caused by low blood levels) or (b) a wave of blood vessel vasodilation (opened blood vessels) followed by a wave of vasoconstriction (narrowed of the blood vessels) across areas of the brain. A similar process was proposed by ME/CFS researchers about 10 years ago.

brain blood flows

Brain blood flow problems appear to play a role in both migraine and chronic fatigue syndrome

CSD depression typically leaves in its wake hypoxia (low blood oxygen levels) and an emphasis, not surprisingly, on anaerobic metabolism with a corresponding increase in lactate levels (which we do see in ME/CFS). CSD is usually a time-limited event, but Baraniuk and Rayhan propose that it’s become chronic in ME/CFS and contributes to the anxiety, fear, fatigue, pain, allodynia and cognitive problems in ME/CFS and similar disorders.

Some alternate hypotheses (Unitary hypothesis, periaqueductal gray matter hypothesis (PAG), neurolimbic hypothesis), all very complex, are proposed.

Maizels’ neurolimbic migraine model actually includes fibromyalgia. Maizels proposes dysfunctional brain networks originating in the brainstem and reaching out to the limbic system (amygdala, insula, anterior cingulate cortex, prefrontal cortex, hypothalamus) produce migraine and fibromyalgia. Brain imaging studies indicated interesting patterns of increased and decreased activity occur in these networks in migraine (and ME/CFS/FM).

Clearly taken by Maizels’ brain network focus, the study authors proposed that future research should focus on network connections, brain blood flows, and integrity of the white matter in the brain. (Baraniuk’s most recent GWI paper focused on the over-activation of the fatigue and pain-producing network in the brain.)


CFS patients “were often unaware of migraine with aura headaches and the potential to use beneficial migraine treatments.” Ravindran and Baraniuk 2011

In the 2011 study, only forty percent of migraine sufferers had been diagnosed, and only a third were being treated with drugs. That thirteen out of the fourteen ME/CFS patients with migraines reportedly responded well to sumatriptan (Imitrex) suggested many people with ME/CFS may be missing out on a valuable treatment option.

Anti-migraine treatments may be beneficial for CFS-related symptoms even in subjects who do not have migraines. Ravindran and Baraniuk 2011

Ravindran and Baraniuk weren’t just talking about migraines, though, when they discussed treatments. Given the similar central nervous system processes they believe are behind ME/CFS, migraine, GWI, and FM, they proposed anti-migraine drugs could be helpful in ME/CFS patients without migraines.

Triptans and Sumatriptan

Triptans include sumatriptan (Imitrex, Imigran, Cinie, Illument, Migriptan), rizatriptan (Maxalt), naratriptan (Amerge, Naramig), zolmitriptan (Zomig), eletriptan (Relpax), almotriptan (Axert, Almogran), frovatriptan (Frova, Migard, Frovamig), and avitriptan (BMS-180,048).

Sumatriptan is a well-known anti-migraine drug that reduces inflammation in arteries and veins in the brain by enhancing 5-HT (serotonin) production. Increased 5-HT production causes over-dilated veins to constrict. Sumatriptan also decreases the activity of nerves called the trigeminal nerves that are associated with cluster headaches.

Interestingly, some research suggests triptans may be affecting the periphery (the body) more than the brain. Triptans’ difficulty in passing the blood-brain barrier has led researchers elsewhere to figure how they’re doing what they’re doing. Studies suggest triptans reduce pain-producing peptides such as substance P in the periphery.

Migraine – Another Difficult To Treat Disorder 

Acknowledging the frustration physicians face with “difficult to treat and understand” ME/CFS/GWI and migraine patients, Baraniuk and Rayhan quote Maizel’s description of the presentation of a typical patient:

“..a middle-aged woman with chronic migraine and medication overuse, as well as fibromyalgia. In addition, there is anxiety and depression, fatigue and insomnia, and the familiar exhaustive list of psychotropics and antiepileptic drugs tried and failed”

Baraniuk and Rayhan propose that Maizels’ neurolimbic model which incorporates dysfunctional serotonergic pathways and central sensitization (i.e., overheated neural networks) is a good place to approach treating these disorders, and they referred to a table produced by Maizels.

stress management diagram

Besides the triptans, both Baraniuk and Maizel’s approach to ME/CFS/FM and migraine emphasized stress reduction

Maizel’s approach is similar to others taken in the field that attempt to tone down central nervous system activity. Other than the use of triptan drugs, his approach relies mostly on behavioral practices to reduce the activation of the neural networks producing central sensitization, arousal, etc.

Maizel proposes that physicians examine issues such as personality styles, stressful lifestyles, and psychiatric comorbidity that can have a profound negative effect on one’s quality of life. Noting that depression and anxiety increase the risk of migraines, Maizel educates patients about the role the limbic system plays in regulating mood, emotion, perceptions, and stress. He includes the following recommendations for physicians:

  • Treat any mood disorders that are present.
  • Use CBT, carefully prescribed activity, acupuncture, tai chi, and other means to retrain the brain and reduce the stress that triggers migraines/relapses and pain.
  • Explore triptan drugs, and topiramate. and other migraine therapies in ME/CFS, GWI, and FM.

Check out Migraines and Chronic Fatigue Syndrome and Fibromyalgia for more on the commonalities between these diseases and treatment options for migraines.

Do You Have Migraines and Not Know It?


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