Hemicrania continua, a rare but severe headache condition, literally means “continuous one-sided headache” in Latin. This chronic condition manifests as an intense, unrelenting pain concentrated on one side of the head, typically around the eye area. It is more common in women.
The condition often presents with distinctive features beyond the constant one-sided pain. Patients frequently experience:
- Redness and tearing of the affected eye
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Nasal congestion and runny nose
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Forehead and facial sweating
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Eyelid swelling
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Pupil size changes
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Restlessness or agitation
The diagnosis of hemicrania continua can be particularly challenging, especially when the only symptom is a one-sided headache. Doctors often misdiagnose it as migraine or tension headache because of its rarity and overlap with other headache types.
What makes hemicrania continua unique is its remarkable response to indomethacin, a powerful non-steroidal anti-inflammatory drug (NSAID). The response to this medication is so dramatic that hemicrania continua is one of two headache types that are called indomethacin-sensitive headaches.
While indomethacin is highly effective, some patients may experience stomach-related side effects. For those who cannot tolerate indomethacin, several alternatives exist:
- Other NSAIDs (though generally less effective)
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Boswellia, an herbal supplement with anti-inflammatory properties
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Botox injections
Chronic paroxysmal hemicrania shares features with hemicrania continua but differs in its pattern. It causes more intense pain attacks lasting minutes but occurring many times throughout the day. Like hemicrania continua, it also responds extremely well to indomethacin.
Read MoreIf you’re one of the millions of people who suffer from migraines, you might be worried about the long-term effects on your brain. Recent studies have suggested that people with migraines might be at higher risk for structural brain changes, such as damage to small vessels in the brain and shrinkage of the brain or brain atrophy.
A recent study published in Cephalalgia by Dutch researchers examined the connection between migraines and brain health in over 4,900 middle-aged and elderly people. The researchers used magnetic resonance imaging (MRI) to study the brains of the participants and assess any structural changes.
The study found that people with migraines were not any more likely to have structural brain changes than those without migraines. There were no significant differences between the two groups in terms of:
- Total brain volume
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Grey matter volume
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White matter volume
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White matter hyperintensity volume (a marker for small vessel disease)
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Presence of lacunes (tiny holes in the brain)
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Presence of cerebral microbleeds (small bleeds in the brain)
This study suggests that having migraines may not increase your risk of developing structural brain changes as you age. This is reassuring news for people who suffer from migraines and are concerned about the long-term effects on their brain health.
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Vitamin B12 deficiency is common in the elderly, vegetarians, people with diabetes, and other chronic conditions. This deficiency can cause neurological, psychiatric, hematological, and other symptoms. It can be a contributing factor to migraines, especially in people who experience visual auras.
If not treated, vitamin B12 deficiency can cause dementia, spinal cord damage, loss of vision, and permanent nerve damage. I check vitamin B12 levels in all of my patients. The blood test, however, is not always reliable. There are reports of severe deficiency with perfectly normal levels. This is why when a deficiency is suspected, additional tests are needed. These are homocysteine and methylmalonic acid levels. These tests can disclose the presence of a deficiency when vitamin B12 level is in the normal range.
To further complicate matters, a report by neurologists at UCSF described a patient with normal blood tests who nevertheless had a severe vitamin B12 deficiency in the brain. They discovered that this patient had antibodies to a receptor (CD320) that is necessary for the uptake of vitamin B12 from the blood into the brain across the blood-brain barrier. The spinal fluid of this patient completely lacked vitamin B12. Her presenting symptoms were difficulty speaking, unsteadiness, and tremor. She had no peripheral manifestations of vitamin B12 deficiency, only those related to the brain. She recovered with high doses of vitamin B12 supplementation and immunosuppressive therapy to reduce the amount of antibodies against the CD320 receptor.
The authors screened a few hundred patients with lupus, multiple sclerosis, and healthy controls. They found these antibodies in 6% of healthy controls, 6% of those with lupus without neurological symptoms, and 6% with multiple sclerosis. Antibodies were present in 21% of patients with lupus who had neurological symptoms.
This newly described condition is called autoimmune B12 central deficiency (ABCD). The role of these antibodies in healthy people is not clear. However, people with unexplained neurological symptoms should have a blood test for homocysteine, methylmalonic acid, and CD320 antibodies.
Read MoreResearchers at a hospital in Northern India reported good results in treating New Daily Persistent Headache (NDPH) with repetitive transcranial magnetic stimulation (rTMS).
NDPH is a type of headache that begins suddenly and persists daily without specific features, distinct MRI presentation, or blood test abnormalities. It can present similarly to chronic migraines or chronic tension-type headaches. While published reports suggest NDPH is difficult to treat, this is often not the case. However, patients who do not respond to initial standard treatments may become discouraged.
- 70% of patients had at least a 50% reduction in headache severity
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Patients gained an average of 11 headache-free days per month
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76% had significant improvements in headache-related disability
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Depression and anxiety scores also improved significantly
The treatment was well-tolerated, with only minor side effects in a few patients. The benefits seemed especially pronounced in patients who had NDPH that resembled chronic migraine.
I never give the diagnosis of NDPH, but diagnose it as a condition it most resembles and treat the person with a wide variety of available options. Many respond. For those who do not, we offer rTMS, a procedure that uses magnetic fields to stimulate nerve cells in the brain. An electromagnetic coil device is placed against the scalp near the forehead. The coil painlessly delivers a magnetic pulse that stimulates the brain with the goal of reducing headache symptoms. The FDA has approved it for the treatment of depression, anxiety, and OCD. We use it for various neurological conditions, including headaches that do not respond to standard therapies. To treat migraines and other types of pain, we usually stimulate not only the left prefrontal cortex, as was done in this study, but also two additional sites that have been reported to help with pain and migraines. These additional sites are either the motor cortex or the occipital cortex, on both sides.
Sometimes, we obtain a functional magnetic resonance imaging (fMRI) scan to better target rTMS. fMRI is a research procedure that is not available commercially (and is not covered by insurance).
Read MoreDr. Messoud Ashina of the Danish Headache Center led a group of European researchers in analyzing the efficacy of migraine medications for treating acute migraine attacks. Their paper published in the British Medical Journal, “Comparative effects of drug interventions for the acute management of migraine episodes in adults: systematic review and network meta-analysis”, looked at 137 randomised controlled trials comprising 89,445 participants allocated to one of 17 active interventions or placebo.
They concluded that “Overall, eletriptan, rizatriptan, sumatriptan, and zolmitriptan had the best profiles, and they were more efficacious than the recently marketed drugs lasmiditan, rimegepant, and ubrogepant.”
When I decided to specialize in treating headaches in 1987, the options for the treatment of acute migraine attacks were very limited. We had NSAIDs, like aspirin and ibuprofen, opioids (narcotics), and ergotamines. Now, we have a cornucopia of options – seven triptans (the first in this group, sumatriptan, was introduced in 1992), three gepants, and one ditan.
Triptans work on serotonin receptors, gepants affect CGRP, and ditan, lasmiditan (Reyvow) works on a different serotonin receptor than triptans.
Over more than 30 years, triptans have proven to be exceptionally safe and effective. In many countries, they are sold without a prescription. Since patents for these drugs have mostly expired, they have become inexpensive.
Gepants were introduced almost five years ago. Ubrogepant(Ubrelvy) and rimegepant (Nurtec) came out first, and more recently, a nasal spray of zavegepant (Zavzpret) was added to this group. They also appear effective and safe, although they have not withstood the test of time like the triptans. And, because they are still protected by patents, they are costly. I don’t think that the prices are too high – if companies cannot recoup literally billions of dollars it takes to get FDA approval, no new drugs will emerge.
It is good to have all these options available because triptans do not work for about 30-40% of patients. For these people, gepants can be life-saving.
In the US, many insurers insist that a patient tries one or two triptans first before they will agree to pay for the more expensive gepants.
In the analysis, eletriptan came out first. However, even though a generic version was introduced in 2017, the cost has not come down as much as for sumatriptan or rizatriptan. Generic sumatriptan can be bought for $.60 a pill, while eletriptan costs $2 a pill. Another important point is that, despite low cost, insurance companies will cover 6 to 12 tablets a month. Some patients don’t realize that if they need more than this amount each month, they could buy extra by paying out-of-pocket, provided their doctor gives them a prescription for a higher amount.
In the US, eletriptan is available in 20 mg and 40 mg strengths. In some European countries, they come in 80 mg strength. The point is that taking two 40 mg tablets at once is not dangerous.
Some patients report that generics do not work as well as branded drugs. Others find that generics made by different manufacturers differ in their efficacy. The manufacturer’s name is always listed on the pill bottle dispensed by the pharmacy. The reason for this discrepancy is not necessarily due to different amounts of the active drug but rather due to inactive ingredients that hold the pill together. Some may not dissolve as fast or as completely as others. This is another reason why taking a higher-than-recommended dose may be necessary.
Triptans are safer than most over-the-counter drugs, such as ibuprofen (Advil), naproxen (Aleve), or Excedrin. They are safer for your stomach, kidneys, and heart.
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Two sets of “designer drugs” have been developed based on our understanding of the neurobiology of migraines. The first, sumatriptan (Imitrex), introduced in 1992, was the pioneer in a class of seven triptan drugs, all targeting serotonin mechanisms. Erenumab (Aimovig), which targets the CGRP (calcitonin gene-related peptide) mechanism, was approved by the FDA in 2018. This class now includes four injectable, three oral, and one nasal drug. Additionally, many older drugs, although not specifically developed for migraine treatment, have proven effective for some patients. Despite these numerous options, a significant minority of patients do not respond to any of these treatments.
This is why the development of drugs targeting different parts of the migraine cascade is so promising. Danish neurologists, led by Dr. Mesoud Ashina, have published results from a phase 2 double-blind study of a new drug that blocks PACAP (pituitary adenylate cyclase-activating peptide).
In this study, patients were divided into two groups, receiving an infusion of a placebo or two different doses of the active drug, currently known as Lu AG09222, developed by the Danish company Lundbeck. In the final analysis, the reduction in migraine days was compared between 94 patients who received a placebo and 97 patients who received the higher dose of the active drug. The higher dose significantly reduced the number of migraine days in the month following the infusion (6.2 vs. 4.2 days reduction). The side effects reported were mild and infrequent.
Phase 2 studies are relatively small and short in duration. The FDA typically requires two large parallel studies involving a total of 1,000 or more patients before considering approval. Therefore, even if Lu AG09222 is found to be safe and effective, it may not receive approval for another 2-3 years.
Read MoreThe diagnosis of migraine still relies on the patient’s description of symptoms. We do not have an objective test to confirm the diagnosis.
Several studies using functional MRI (fMRI) attempted to identify people with migraines. A new study published by Korean doctors in The Journal of Headache and Pain used a different imaging technique to achieve this goal.
The researchers used diffusion MRI, a technique that focuses on the movement of water molecules within the brain’s tissues (fMRI measures blood flow to different areas of the brain). It is particularly useful for mapping the brain’s white matter tracts, which are the pathways that connect different brain regions.
47 patients with migraine were compared to 41 healthy controls
Significant differences were found in brain regions such as the orbitofrontal cortex, temporal pole, and sensory/motor areas.
Changes in connections between deeper brain structures (like the amygdala, accumbens, and caudate nuclei) were also noted.
Using machine learning, the researchers could distinguish between migraine patients and healthy individuals based on these brain connectivity features.
Hopefully, larger studies and easier access to advanced imaging techniques may eventually lead to an objective test of migraines. More importantly, identifying specific connectivity patterns may lead to more individualized treatments. These could be treatments with pharmaceuticals or neurostimulation techniques such as transcranial magnetic stimulation (TMS), which we use in our clinic.
Read MoreGiven enough triggers, almost anyone can develop a migraine. There is a very good chance that even someone who has never had a migraine to become sleep-deprived, dehydrated, drunk, and stressed will develop a migraine headache. However, I have encountered people who told me that they have never had a headache and cannot even imagine what a headache would feel like.
Scientists have discovered why some people never get headaches. Researchers studied the DNA of nearly 64,000 people in Denmark, including about 3,000 who reported never having had a headache. The researchers found a specific area in a gene called ADARB2 that seems to protect against headaches. People with a certain variation in this gene were 20% more likely to be completely headache-free. ADARB2 is mostly active in the brain, particularly nerve cells that reduce brain activity. However, scientists don’t fully understand how this gene works yet.
While this discovery is exciting, more research is needed to confirm how ADARB2 helps prevent headaches. This study is the first to examine the genetics of being headache-free rather than focusing on what causes headaches. It opens up a new approach to understanding and potentially treating headache disorders.
Read MoreAthletes have been using creatine supplementation for over 30 years. It seems to improve the energy supply to muscle tissues and increase fat-free mass. Creatine also supplies energy to nerve cells in the brain. Taking a creatine supplement increases the levels of creatine in muscles and the brain.
A review of six studies suggested that creatine improves short-term memory, intelligence, and reasoning. Creatine did not improve any cognitive abilities in young people. Vegetarians benefited more than non-vegetarians in memory tasks.
Greek doctors published a report, Prevention of traumatic headache, dizziness and fatigue with creatine administration. A pilot study. They studied 39 patients who sustained a severe traumatic brain injury. There were 19 patients in the control group and 20 in the active group. The active group was given 0.4 g/kg of creatine. Treatment was administered within 4 hours of injury and was continued for 6 months. This treatment improved the duration of post-traumatic loss of memory, the duration of being on a respirator, and the duration of stay in an intensive care unit. They also showed improvement in headaches, dizziness, and fatigue. No side effects were reported.
Some studies suggest that creatine can improve bone health. Here is what WebMD says about creatine:
“While most people get low amounts of creatine by eating seafood and red meat, larger amounts are found in synthetic creatine supplements. Your pancreas and kidneys can also make around 1 gram of creatine each day. Creatine is one of your body’s natural energy sources.
Nearly 95% of the creatine in your body is stored in your skeletal muscles and is used during physical activity. As a dietary supplement, creatine is commonly used to improve exercise performance in athletes and older adults.”
There is not enough evidence to routinely recommend creatine for the treatment of migraine headaches. I do, however, recommend to my older patients taking 5 to 7 grams of creatine an hour before or after exercise. I am 67 and do take it when I exercise.
Read MoreCandesartan ((Atacand) is a blood pressure medication in the class of angiotensin receptor blockers (ARBs). A recently published study involving 86 patients confirmed that candesartan can improve migraines. This was not a double-blind but rather an observational study, meaning that the results were not as reliable. However, the study is worth publicizing since candesartan is often overlooked as an effective migraine drug.
Here is more about candesartan from my previous post:
Candesartan was first shown to work for the prevention of migraine headaches in a 60-patient Norwegian trial published in JAMA in 2003. This was a double-blind crossover trial, which means that half of the patients were first placed on a placebo and then switched to candesartan and the second group started on candesartan and then were switched to placebo. This trial showed that when compared to placebo, 16 mg of candesartan resulted in a very significant reduction in mean number of days with headache, hours with headache, days with migraine, hours with migraine, headache severity index, level of disability, and days of sick leave. Candesartan was very well tolerated – there was no difference in side effects in patients taking the drug and those taking the placebo.
In another trial, the researchers compared candesartan to placebo as well as to propranolol, which is an FDA-approved blood pressure drug for the prevention of migraines. This trial in 72 migraine sufferers compared 16 mg of candesartan with placebo and 160 mg of propranolol. Candesartan and propranolol were equally effective in reducing migraine days per month and both were significantly more effective than placebo.
Read MoreA new study from Mayo Clinic researchers, published in The Journal of Headache and Pain, has examined the brain changes associated with acute post-traumatic headaches (PTH). These headaches can occur after a head injury or trauma and can be debilitating. The study involved 60 participants with acute PTH and 60 age-matched healthy controls. Using functional MRI (fMRI), the researchers found two key differences in the brains of PTH patients compared to healthy individuals.
Increased Iron Accumulation in Specific Brain Regions
First, the PTH patients showed higher levels of iron deposition in two brain areas: the left posterior cingulate and the bilateral cuneus regions. These areas are involved in various functions, including pain processing, attention, and visual processing. The accumulation of iron in these regions may disrupt normal brain function and contribute to the development and persistence of post-traumatic headaches.
Abnormal Functional Connectivity Patterns
Secondly, the researchers observed stronger functional connectivity between the bilateral cuneus (the visual processing area) and the right cerebellum (a region involved in motor control and coordination, and other functions) in PTH patients compared to healthy controls. Functional connectivity refers to the communication and synchronization between different brain regions. The abnormal connectivity patterns seen in PTH patients suggest disruptions in the brain networks responsible for processing sensory information, including pain signals.
Implications for Targeted Therapy
While these findings may have lacked utility in the past, they now have important implications for the treatment of post-traumatic headaches. We have been treating patients with repetitive transcranial magnetic stimulation (rTMS), a non-invasive technique that can modulate brain activity in specific regions. By stimulating the areas with abnormal connectivity, rTMS may help restore normal brain function and alleviate headache symptoms and other neurological and psychiatric symptoms. When possible, we perform fMRI scans on individual patients to identify the specific brain regions involved in their headache disorder. However, fMRI is still only a research tool, and when individual fMRI data is not available, studies like this one provide information on common brain changes associated with post-traumatic headaches that can be targeted with TMS.
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