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Restless leg syndrome (RLS) has been reported to be more common in patients with migraines. I wrote about this association in a previous post about 4 years ago. Another study, just published in The Journal of Headache and Pain confirms this association.

RLS is a common condition that often goes undiagnosed. This is in part due to the fact that RLS begins in childhood and it often runs in the family, so it is not perceived as an illness.

The new study involved 505 participants receiving outpatient headache treatment. The researchers collected information on experiences of migraine, RLS, sleep quality, anxiety, depression, and demographics. Participants were divided into low-frequency (1–8/month), high-frequency (9–14/month), and chronic (>15/month) headache groups.

Analysis revealed that with an increase in migraine frequency the occurrence of RLS also increased, particularly in those who had migraines with auras. Anxiety and sleep disturbance was also associated with RLS.

Sometimes the diagnosis of RLS is very easy to make – a person who constantly shakes his or her foot, usually has it. However, in some people the excessive leg or body movements occur only in sleep, so the diagnosis is less obvious to the doctor, but not to the bed partner who is constantly kicked and woken up by these movements. One of my patients could not sleep in the same bed with his wife, because he would move and kick her all night long. After he started taking ropinirole, one of the medications for RLS, he reported that he was able to sleep in the same bed with his wife for the first time in 20 years. If the diagnosis is in doubt, an overnight sleep study can confirm the diagnosis.

Unfortunately the person with RLS suffers much more than the bed partner. Moving all night means not getting good quality sleep and being tired all day. Treating RLS leads not only to improved sleep, but also to an overall improvement in the quality of life.

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Restless leg syndrome (RLS) is more common in women who also suffer from migraines, according to a new study published in the journal Cephalalgia. Women with migraines are 20% more likely to also have RLS. This study involved 31,370 US health professionals making its findings highly reliable. In my previous post 5 years ago I mentioned that RLS, by disrupting normal sleep, may increase the frequency and severity of migraines, but at that time we did not know that these two conditions are connected. Possible causes of this association include the fact that disturbance of metabolism of iron and dopamine in the brain is thought to play a role in both conditions. People who have symptoms of RLS should be tested for iron and vitamin B12 deficiency which can cause similar symptoms. A sleep study is sometimes necessary to confirm the diagnosis of RLS. This study involves sleeping in a sleep lab with wires attached to the scalp, monitors measuring breathing and video camera recording movements of legs and body. Most major hospitals have a sleep lab and it is usually covered by insurance.
Fortunately, we have many effective drugs to treat RLS – Requip (ropinirole), Mirapex (pramipexole), Horizant (gabapentin), Neupro patch (rotigotine), as well as opioid drugs, such as Vicodin (hydrocodone), Percocet (oxycodone), and other. Horizant is a long-acting form of gabapentin, which is available in a short-acting form as a generic, much cheaper form. The advantage of gabapentin (also known as Neurontin and Gralise) is that it has also been shown to prevent chronic migraine, so this one drug can potentially treat RLS and migraine.

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Cluster headaches are much less common than migraines (less than a million vs 36 million sufferers), but are arguably the most painful type of headaches a man can experience. And it is usually a man because cluster headaches are thought to be 3-5 times more common in men. However, a study just published in Neurology suggests that the ratio of men to women is closer to 2:1.

This study by Danish researchers also established that women suffering from cluster headaches are more often misdiagnosed than men – 61% vs 46%. Consequently, it takes a year longer for a woman to be diagnosed than for a man – 6.5 years vs 5.5 years. But considering how devastating these headaches can be, these numbers are terrible for both sexes.

Cluster headaches get their name from the fact that they occur in clusters – daily or more frequent attacks lasting one to three hours for a period of a month or two, each year and often at the same time of year. One surprising finding of the study is that women are more likely to have chronic cluster headaches (no break from attacks for more than a month) – 44% vs 32%.

The reason for such high rates of misdiagnosis and long delays in diagnosing cluster headaches is that it is a relatively rare type of headaches and that it is easy to mistake cluster for a migraine or a sinus headache. Cluster headache is always one-sided and centers in the eye, which is common with migraines. It is usually accompanied by a runny nose (and tearing with redness of the eye) as occurs with a sinus headache.

But cluster headaches also have very distinctive features that should make the diagnosis easy, if only doctors asked a few questions. I’ve had a fair number of patients who diagnosed themselves after being misdiagnosed by doctors. During a cluster attack patients tend to be restless, pacing around, hitting their fist or even their head against walls, and sometimes screaming from pain, while migraine sufferers tend to stay very quiet since every movement, sound, and light worsen the pain. The fact that these occur every night for an hour or two and then resolve on their own is also a telltale sign. Migraine pain lasts for at least 4 hours and often for a couple of days without a break. Sinus headaches do not come and go and are easy to rule out by a CAT scan, a standard equipment in every emergency room and cluster sufferers do often end up in an ER.

Fortunately, once the correct diagnosis is made, cluster headaches can be treated very effectively in most patients. Some of the treatments overlap with migraines, such as sumatriptan injections, magnesium infusions, occipital nerve blocks, and Botox injections, but other help only cluster headaches. These include a 10-day high-dose course of steroids, oxygen inhalation, high-dose verapamil, lithium, and other.

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Nausea is a very common symptom that accompanies migraine attacks. Effective treatment of migraine with a drug like sumatriptan often stops the headache, nausea, and other associated symptoms. However, sometimes pain subsides, while nausea does not, or nausea is much more bothersome than the headache. Nausea can also be a side effect of the most effective injectable migraine drug, dihydroergotamine (DHE-45). We often administer this drug in our office after other injectable drugs (magnesium, sumatriptan, ketorolac, dexamethasone, etc) fail. If nausea is already present, we will always give an intravenous injection of a nausea drug such as ondansetron (Zofran) or metoclopramide (Reglan) before giving DHE. Sometimes these drugs are ineffective in preventing nausea and vomiting induced by DHE and we have to look for other options.

Phenothiazine family of drugs, including prochlorperazine (Compazine), chlorpromazine (Thorazine), and promethazine (Phenergan) are very old and effective anti-nausea drugs. However, they have a potential for a rare but devastating side effect, which consists of persistent involuntary movements of the face (grimacing and lip smacking) and body. The onset of this side effect can be delayed, which is why it is called tardive dyskinesia. It is not unusual for these drugs to cause an immediate severe and very unpleasant restlessness (akathisia), which patients sometimes describe as wanting to crawl out of one’s skin. Metoclopramide (Reglan) can also cause these side effects, but less often.

Ondansetron (Zofran) does not cause any such side effects and should be the preferred drug for nausea of migraine, although it is only approved for nausea caused by chemotherapy or radiation and for post-surgical nausea. Since it has become generic and inexpensive, it can be used for other causes of nausea, including migraines. It is available as an injection or as a tablet.

Aprepitant (Emend) is an anti-nausea drug that has a totally different mechanism of action than the medications described above, so it is possible that it can help when other drugs do not or when other drugs cause side effects.

A study just published in Neurology by Dr. Denise Chou and her colleagues describes the use of oral aprepitant in the treatment of DHE-induced nausea in hospitalized patients.

The authors reviewed hourly diary data and clinical notes of patients admitted to the hospital for the treatment of refractory migraine headaches (status migrainosus) with DHE infusions between 2011 and 2015.

They identified 74 such patients, of whom 24 had daily diaries. In 36 of 57 cases in which aprepitant was given, there was a 50% reduction in the number of other anti-nausea medications given to patients. Of 57 patients, 52 reported that the addition of aprepitant improved nausea. Among 21 of 24 patients with hourly diary data, nausea scores were reduced. In all 12 patients with vomiting aprepitant stopped it. Aprepitant was well tolerated and caused no side effects.

The authors concluded that aprepitant can be effective in the treatment of refractory DHE-induced nausea and vomiting. They also suggested that perhaps this drug could be used for nausea of migraine even when DHE is not given. The only problem, and it is a very big problem, is the cost. This drug is not going to be available in a generic form until 2018. A single capsule of Emend costs $105 with a coupon you can get on GoodRx.com. Without a coupon, it is $145. A single vial for injection costs $345, so we are not going to use this drug for nausea due to migraine or DHE for at least two years, when cheaper generic copies become available.

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Post-concussion symptoms have long been thought to be more severe and prolonged in people who have pre-existing psychological problems. This has been shown to be the case in the military personnel. A new study confirmed this observation in the first prospective study. Over 2,000 high school and college athletes in Wisconsin were asked to answer 18 questions (Brief Symptom Inventory-18, or BSI-18) and then were followed for three years. The 18 questions, which are listed below, addressed the presence of anxiety, panic attacks, depression, and somatization (excessive bodily sensations). In the ensuing three years, 127 athletes sustained a concussion. The concussion had to be diagnosed by a licensed athletic trainer according to the Department of Defence definition, which includes alteration of mental status with associated headache, nausea, vomiting, balance difficulties, dizziness, cognitive difficulties, and other. These athletes were again evaluated two and six weeks later. Eighty percent of concussed athletes were men. The mean duration of symptoms was five days. Ninety five percent of them recovered completely within a month. High somatization score on the BSI-18 questionnaire predicted prolonged duration of symptoms, while no correlation was found with the years of playing a sport, the type of sport (most played football), number of prior concussions, migraines, ADHD, or the grade point average. Another factor that delayed recovery was the initial symptom severity after the concussion. Most of the concussions were mild with less than 10% of athletes losing consciousness.

An interesting and unexplained fact, not examined in this study, is that milder concussions tend to cause more severe symptoms than severe ones.

This was a very thorough study, but it was relatively small, so it is possible that other pre-concussion factors may also delay recovery. One such factor is pre-existing migraines. I see many patients, adults and children, who suffered from migraines and after a concussion have worsening of their migraines or new daily persistent headaches. If they themselves have never suffered from migraines, often their mother or siblings have a history of migraines, suggesting genetic predisposition to migraines.

Treatment of post-concussion symptoms, include typical therapies employed in migraine sufferers, including aerobic exercise, biofeedback, magnesium supplementation, Botox injections, and a variety of medications.

Brief Symptom Inventory-18

The Somatization dimension
01. Faintness or dizziness
04. Pains in heart or chest
07. Nausea or upset stomach
10. Trouble getting your breath
13. Numbness or tingling in parts of your body
16. Feeling weak in parts of your body
The depression dimension
02. Feeling no interest in things
05. Feeling lonely
08. Feeling blue
11. Feeling of worthlessness
14. Feeling hopeless about the future
17. Thoughts of ending your life
General anxiety
03. Nervousness or shakiness inside
06. Feeling tense or keyed up
15. Feeling so restless you couldn’t sit still
Panic
09. Suddenly scared for no reason
12. Spells of terror or panic
18. Feeling fearful

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Cluster headaches cause more severe pain than any other type of headaches. Some patients even call them suicide headaches because they provoke thoughts of suicide. The name comes from the fact that they occur in clusters – every day for a couple of months and then they go away for a year or longer. In those with chronic cluster headaches they never go away. The headaches are brief – anywhere from 30 minutes to 3 hours. They are always one-sided, with pain usually around the eye, and are accompanied by tearing, nasal congestion, and sometimes restlessness. More men than women suffer from them.

Treatment of cluster headaches can be very effective. A 10-day course of prednisone or an occipital nerve block can abort the entire cluster. We also have preventive drugs, such as a blood pressure medicine, verapamil (used in high doses), epilepsy drugs, and lithium. These are taken daily to prevent headaches. To treat individual attacks, inhalation of 100% oxygen under high flow, zolmitriptan nasal spray (Zomig NS), and sumatriptan (Imitrex) injections can be true life savers.

Some of the alternative therapies that have been reported to help include melatonin, intranasal capsaicin (hot pepper extract), and an herbal product, Boswellia (Nature’s Way is a good brand for herbals).

Unfortunately, there are some cluster headache sufferers who do not respond to any of these treatments. We even treated some patients with intravenous histamine, which requires hospital admission and two of my patients were implanted with a vagus nerve stimulator (with good relief).

Some cluster patients have been found to have low testosterone levels and treating them with testosterone seems to help.

This testosterone connection led to trials of a fertility drug, clomiphene citrate (Clomid). Clomiphene enhances testosterone production and binds to hypothalamic estrogen receptors, which is why it was considered as a treatment for cluster headaches. A second case of successful treatment of cluster headaches with Clomid has just appeared in the journal Headache. This was a case of a 65-year-old man with a 17-year history of chronic cluster headaches who did not respond or had significant side effects to many cluster headache preventive medications including verapamil, lithium, valproic acid, topiramate, baclofen as well as greater occipital nerve blocks and inpatient hospitalization.

The patient experienced 3-5 headaches per day. On Clomid (100 mg/day) he became 100% pain-free and remained so for three and half years with only mild fatigue as a side effect. He then had cluster headache recurrence and did well on gabapentin for another 3 years, but then his headaches returned. Clomiphene was restarted, and he became pain-free once again.

Clomid should be considered when the usual preventive drugs for cluster headaches are ineffective.

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Parkinson’s disease (PD), parkinsonian symptoms, and restless leg syndrome (RLS) are more common in people who in middle age suffered from migraines with aura. Those suffering from migraine without aura in their midlife had increased risk of having symptoms of Parkinson’s and RLS, but not PD. These are the findings of a large study of residents of Reykjavik, Iceland who were born between 1907 and 1935. These residents had been followed since 1967. Headaches were classified based on symptoms assessed in middle age. From 2002 to 2006, 5,764 participants were reexamined to assess symptoms of parkinsonism, diagnosis of PD, family history of PD, and RLS.

People who suffered from migraines, particularly migraine with aura, were in later life more likely than others to report parkinsonian symptoms and diagnosed to have PD. Women with migraine with aura were more likely than others to have a parent or sibling with PD. Late-life RLS was increased in those with headaches generally.

The authors concluded that there may be a common vulnerability to, or consequences of, migraine and multiple indicators of parkinsonism.

There are no proven ways to prevent PD, but eating more fruits and vegetables, high-fiber foods, fish, and omega-3 rich oils (or taking an omega-3 supplement, such as Omax3) and avoiding red meat and dairy may have some protective effect against PD.

Intensive research into the causes and treatment of Parkinson’s disease, supported by Michael J. Fox and Sergey Brin of Google among others, should lead to true breakthroughs in the next few years.

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Sleep deprivation is a very common trigger of migraine and tension-type headaches. Scientists have always wondered about the purpose of sleep. We know that sleep helps strengthen our memories. New research suggests that sleep is also needed for other housekeeping chores, such as cleaning junk out of our brains. Literally, the brain rids itself of damaged proteins during sleep. It appears that poor sleep quality leads to accumulation of these proteins, which can lead to a higher risk of Alzheimer’s disease.

Another recent study showed that people with insomnia tended to have smaller brain volume in certain regions of the brain, particularly frontal lobes.

Other research showed that a variety of psychiatric illnesses also lead to a reduced brain volume. The frontal lobes are necessary for planning our actions, mood, and affect.

Veterans with post-traumatic stress disorder (PTSD) frequently complain about sleep difficulties and have documented high rates of sleep disorders

In the latest study, the researchers scanned the brains of 144 veterans using magnetic resonance imaging (MRI).

The participants with poor sleep quality had less frontal lobe gray matter than vets who reported sleeping well.

These veteran had other psychological disorders, in addition to the sleep disorder. Half of them abused alcohol, 40 percent had depression and 18 percent had PTSD.

The connection between sleep disorders and the brain volume was not affected by psychiatric medications.

The researchers speculated that these findings are not necessarily limited to veterans. However, they were careful to stress that their findings do not prove that there is a cause and effect relationship between sleep quality and brain volume. It is possible that something else is causing both sleep problems and shrinkage of the brain or that shrinking of the brain causes sleep disturbances and not the other way around.

What is indisputable is that we all need good night’s sleep to function normally, avoid headaches, accidents, and be happy. Most people need 7 hours of sleep, but there are some who need only 5 or 6 and others, 8 to 9 hours. A very small percentage of people function perfectly well with 3 or 4 hours of sleep. On the other hand, some people do not feel rested no matter how long they sleep. Those usually suffer from a sleep disorder, such as sleep apnea, restless leg syndrome, narcolepsy, and other. The diagnosis is made through a sleep study. Treating the underlying sleep disorder often leads to a dramatic improvement in the quality of life, including an improvement in migraine and tension-type headaches.

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A severe migraine attack can sometimes land you in an emergency room. With its bright lights, noise, and long waits, it is the last place you want to be in. To add insult to the injury, some doctors will think that you are looking for narcotic drugs and treat you with suspicion, while others will offer ibuprofen tablets. It is hard to think clearly when you are in the throes of a migraine, so you need to be prepared and have a list of treatments you may want to ask for, just in case the ER doctor is not good at treating migraines.

If you are vomiting, first ask for intravenous hydration and insist on having at least 1 gram of magnesium added to the intravenous fluids. Everyone with severe migraines should have sumatriptan (Imitrex) injection at home since it often eliminates the need to go to an ER in the first place. If you haven’t taken a shot at home, ask for one in the ER. The next best drug is a non-narcotic pain medicine, ketorolac (Toradol) and if you are nauseous, metoclopramide (Reglan). Do not let the doctor start your treatment with divalproex sodium (Depakene, drug similar to an oral drug for migraine prophylaxis, Depakote) or opioid (narcotic drugs) such as demerol, morphine, hydromorphone and other.

This post was prompted by an article just published in the journal Neurology by emergency room doctors at the Montefiore Hospital in the Bronx. It was a double-blind trial which compared intravenous infusion of 1,000 mg of sodium valproate with 10 mg metoclopramide, and with 30 mg ketorolac. They looked at relief of headache by 1 hour, measured on a verbal 0 to 10 scale. They also recorded how many patients needed another rescue medication and how many had sustained headache freedom.

Three hundred thirty patients were enrolled in the study. Those on divalproex improved by a mean of 2.8 points, those receiving IV metoclopramide improved by 4.7 points, and those receiving IV ketorolac improved by 3.9 points. 69% of those given valproate required rescue medication, compared with 33% of metoclopramide patients and 52% of those assigned to ketorolac. Sustained headache freedom was achieved in 4% of those randomized to valproate, 11% of metoclopramide patients, and 16% receiving ketorolac. In the metoclopramide arm, 6% of patients reported feeling “very restless”, which can be a very unpleasant side effect of this drug.

The authors concluded that the valproate was less efficacious than either metoclopramide or ketorolac. Metoclopramide was somewhat better than ketorolac but it also had more side effects.

To summarize, ask the doctor to start with hydration and magnesium, then sumatriptan injection, followed by metoclopramide and ketorolac, if needed. If the above treatments do not help, we also give dexamethasone (Decadron, a steroid medication) and DHE-45 (dihydroergotamine). All these medications can be administered in the office and we always tell our patients not to go to an ER and to come into the office if the attack occurs during our office hours.

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Nausea of migraines responds to an acupressure device, according to two German doctors who presented their findings last week at the International Headache Congress in Boston. I spoke to one of the authors, Dr. Zoltan Medgyessy about his study. The study included 41 patients, whose average age was 47 years. They had been suffering from migraines for on average 26 years and had experienced an average of 33 migraine
days over the previous three months. The average migraine pain intensity was 7 on a scale from 0 to 10; the average intensity of nausea was 6 on a 1-10 scale. Patients were instructed to use the device (Sea Band) instead of taking nausea medication during their next migraine attack and to complete and return a migraine attack diary. After using the acupressure band, 34 (83%) patients noticed a reduction of nausea and 18 (44%) reported a significant improvement in nausea. The average intensity of nausea after therapy was 3. The relief of nausea was reported after an average of 29 minutes. The average duration of the migraine attacks was 22 hours. The Sea Bands were worn on average for 18 hours. Forty patients (98%) reported that they would use Sea Band during migraine attacks again. The authors concluded that the use of an acupressure band can reduce migraine-related nausea. The advantage of this therapy is that it is drug-free and has no risks
or side-effects such as dizziness, fatigue, or restlessness seen with drugs. Its effect is rapid, and it is easy and it is inexpensive to use (in the US, $6 to $10). To prove that this method works beyond just placebo effect we need a blinded trial comparing anti-nausea medication with Sea Bands. I do recommend Sea Bands or a similar device, Psi Band for my migraine patients. A controlled trial in 60 women showed that Sea Bands relieve morning sickness of pregnancy (nausea and vomiting of pregnancy), which suggests that the relief we see in migraine patients is also real and not just due to placebo.

Art credit: JulieMauskop.com

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Prodrome refers to symptoms that precede an actual attack of migraine. Migraine aura also precedes an attack, but it occurs 20 to 60 minutes before the headache and typically consists of visual disturbances or partial visual loss. Prodrome typically is a period of 24 to 48 hours before a migraine attack and it can consist of a wide variety of symptoms. Many people are aware that these symptoms indicate an impending migraine attack, but some are not. Some people tell me that when they feel unusually full of energy, very happy, and creative they realize that they will get a headache the next day. And some realize that what was happening to them was a prodrome only in retrospect, even after having all of the same symptoms repeat themselves many times. Not many people experience prodrome and its features are varied. Here are some of the symptoms reported in the prodrome period:
Depression
Euphoria
Irritability
Restlessness
Hyperactivity
Fatigue
Drowsiness
Difficulty concentrating
Neck or other muscle stiffness
Feeling hot or cold
Increased thirst
Increased urination
Food cravings
Loss of appetite
Yawning
Tearing
Constipation
Diarrhea
Fluid retention
Sensitivity to light and/or sound
If you do experience a prodrome and are aware of it while it is happening, taking an anti-inflammatory medication (Advil, Aleve, Migralex) or, if that does not work, a triptan may prevent an attack or at least make it milder.

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Restless leg syndrome (RLS) affects 10% of the population with 3% suffering from severe symptoms. Patients suffering from RLS complain of difficulty falling asleep because of uncomfortable sensation in their legs which is temporarily improved by moving their legs or getting up and walking around. The movement of the legs persists in sleep and interferes with the deep restful stages of sleep leading to tiredness during the day. Many patient do not realize they have a problem because they’ve had it all their lives and because one of their parents also had it.Researchers reporting in the recent issue of journal Nature Genetics say they have found proof of the genetic nature of RLS. However, not all patients with these symptoms have RLS. Iron deficiency, peripheral nerve damage and antidepressant medications can cause symptoms of RLS. Another sleep disorder, such as sleep apnea can at times mimic RILS and a sleep study may be needed to establish the diagnosis.Treatment of RLS involves the use of medications such as Requip, Mirapex, which belong to a category of drugs called dopamine agonists (they are also used to treat Parkinson’s disease, but these two conditions are not related). Some epilepsy drugs, including Neurontin and Topamax and particularly opioid analgesics, such as hydrocodone and oxycodone can be effective.Sleep deprivation or poor quality of sleep can be a major trigger for migraine headaches. We see many patients with RLS at the NYHC and treating their RLS will often improve their headaches.

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