Archive
Trigeminal and other neuralgias

It’s an honor to have contributed, alongside Andrew Blumenfeld and Sait Ashina, a chapter on Botox injections to the upcoming textbook Headache and Facial Pain Medicine. Edited by Sait Ashina of Harvard Medical School and published by McGraw Hill, the book is set for release in 2025 but is already available on Amazon.

The book includes chapters on Primary Headaches, Secondary Headaches, Facial Pain and Cranial Neuralgias, Special Treatments and Procedures, Special Populations, and Special Topics. It is an excellent textbook for health care providers.

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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

  • Nasal congestion and runny nose

  • Forehead and facial sweating

  • Eyelid swelling

  • Pupil size changes

  • 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)

  • Boswellia, an herbal supplement with anti-inflammatory properties

  • 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.

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We use a neuronavigation system from Soterix (on the left) for precise targeting of transcranial magnetic stimulation (TMS). And we use the most advanced TMS machine from MagVenture (on the right) to treat chronic pain, migraines, fibromyalgia, and other neurological conditions.

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Botox has been shown to relieve the pain of trigeminal neuralgia (TN). TN is an excruciatingly painful and debilitating condition. The most common cause of TN is compression of the trigeminal nerve by a blood vessel. This tends to occur in older people in whom blood vessels may harden with age. The definitive treatment of TN is surgical decompression of the trigeminal nerve. This is done by opening the skull and placing a Teflon patch between the nerve and the blood vessel. Several medications and invasive procedures directed at the peripheral nerve have been also proven effective. They are usually tried before surgery because of the risk of complications from surgery.

Besides the elderly, younger people with multiple sclerosis (MS) are also predisposed to developing TN. The mechanism is somewhat different. There is less or no compression of the nerve but rather there is damage to myelin, a sheath that covers the nerve inside the brainstem. Myelin prevents cross-talk between nerve fibers, which is the cause of the pain.

According to a report by Turkish neurologists that was recently published in Headache, Botox can relieve the pain of TN in MS patients as well. They compared the response to Botox in 22 patients with primary TN and 31 with MS-related TN. Ten patients of 22 in the first group and 16 out of 31 in the second group improved with Botox. Patients who had interventional treatments in the past did not respond as well. Those who had mild continuous pain between bouts of severe pain were more likely to respond to Botox.

Botox is not the first-line treatment for TN. Medications such as carbamazepine and oxcarbazepine are. However, Botox is a very safe treatment and should be tried before considering surgery and other invasive procedures.

 

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A case report presented at the annual meeting of the American Headache Society described a patient with trigeminal neuralgia (TN) whose pain responded well to rimegepant (Nurtec). Rimegepant is a drug approved for the acute and preventive treatment of migraines. This patient did not obtain relief from surgery and several medications. He was taking 300 mg of oxcarbazepine, buprenorphine (narcotic) patch, and up to 120 mg of oxycodone with partial relief. Within 12 hours of starting rimegepant he was pain-free. In the six months of taking rimegepant he experienced very infrequent and mild pain.

There have been several reports indicating that injections of CGRP monoclonal antibodies such as erenumab can relieve the pain of TN. So it is not surprising that an oral CGRP drug helped this patient.

I’ve treated several TN patients with CGRP antibodies. One such patient has been receiving injections of galacanezumab for over 3 years. He requires injections of 240 mg every 3 weeks and also has to take daily medications. This combination has allowed him to be fully functional and to keep his job. I may now try him on an oral CGRP drug.

In addition to rimegepant, there are two other oral CGRP drugs – ubrogepant (Ubrelvy) and atogepant (Qulipta). They are very similar but many patients have a clear preference for one over the others. It may be worth trying them all if the first drug is not fully effective. A major obstacle to using these medications “off label” for TN is their high cost.

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Trigeminal neuralgia (TN) is an extremely painful and often debilitating condition. Many people respond to the standard therapy with epilepsy drugs such as carbamazepine (Tegretol) or oxcarbazepine (Trileptal). Botox injections can be helpful as well. A significant minority of patients, however, do not respond to these treatments and sometimes require brain surgery.

Fortunately, we have a new class of drugs that has allowed some of my patients to avoid having an operation. These drugs are CGRP monoclonal antibodies (mAbs). They have been approved by the FDA only for the prevention of migraine headaches, so their use for TN is considered to be “off-label”.

The first case series was reported in 2019 by the Cleveland Clinic doctors. They found that six out of eight TN patients had a good response to erenumab (Aimovig).

A group of Israeli physicians published another case series in the current issue of Neurology. They found that nine out of ten TN patients obtained very good relief from erenumab.

Erenumab was the first CGRP mAb. It was approved in May of 2018. Another two, galcanezumab (Emgality) and fremanezumab (Ajovy) were approved about six months later. These are given by a monthly subcutaneous injection. About a year ago, an intravenous CGRP mAb, eptinezumab (Vyepti) was also approved. These four drugs are very similar. However, some patients find one to be more effective than others. I’ve found this to be true not only in migraine patients but also in those with TN. Erenumab is slightly different in its mechanism of action and it is the only one that has a warning about the potential for causing severe constipation and increased blood pressure. Since TN patients tend to be older and more prone to these side effects, I prefer galcanezumab or fremanezumab. Unlike eptinezumab, they can be self-administered.

Off-label use is totally legitimate. However, insurance companies are not likely to pay for an expensive drug that is not explicitly approved by the FDA for a specific indication. And these drugs are not cheap – about $600 to $700 for each monthly shot. Because of the competition among pharmaceutical companies, they provide us with plenty of free samples (except for eptinezumab). TN is a relatively rare disorder so we can provide free samples to all of our TN patients who respond to these drugs. This is true for most neurologists’ private offices. This may not be true in big hospitals where sampling is not allowed.

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Trigeminal neuralgia (TN) is an extremely painful condition. Patients describe the pain as electric shocks going through the face. The most common or classic form of TN is caused by the compression of the trigeminal nerve as it exits the brainstem by a blood vessel. TN can also be caused by multiple sclerosis (MS).

The pain of TN can be debilitating. Some people are unable to eat because of pain and become malnourished. The pain can interfere with speech. In some, it occurs unprovoked. In many, it leads to depression.

The first-line treatment is epilepsy drugs. These include carbamazepine (Tegretol) and oxcarbazepine (Trileptal). We also use Botox injections and the new preventive migraine drugs – CGRP monoclonal antibodies. If drugs and Botox fail, radiofrequency destruction of the nerve can be of help. When none of this helps, surgery can be very effective.

The so-called microvascular decompression surgery involves opening the skull and placing a Teflon patch between the nerve and the blood vessel which presses on the nerve. Since TN in people with MS is not caused by the compression of the nerve, surgery is rarely undertaken.

This is a very delicate surgery and should be performed by a neurosurgeon who has done many of such operations (yes, it’s a conundrum – how do surgeons become experienced if nobody wants to be one of their early cases). Sometimes, even if surgery is performed well, the pain persists.

Fortunately, a group of Canadian researchers found a way of predicting who is likely to respond to decompression surgery. In a study just published in the journal Pain, they described a special MRI scanning technique that predicted the success of surgery with high accuracy. They discovered that if the trigeminal nerve fibers are disrupted inside the brainstem rather than after they exit the brainstem, surgery was much less likely to help. This applied to both patients with classic TN and TN due to MS.

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The annual scientific meeting was held last weekend in Philadelphia. The largest number of presentations was about the CGRP drugs, both monoclonal antibodies (mAbs) for the prevention and soon to be approved oral medications for the abortive treatment of migraine attacks. In addition to the three currently available mAbs, erenumab (Aimovig), fremanezumab (Ajovy), and galcanezumab (Emgality), which are self-injected subcutaneously every month (Ajovy can be given every 3 months), a fourth intravenous mAb, eptinezumab, which is given every 3 month, is likely to come out early next year.

Two oral CGRP drugs that are in development are taken as needed for an individual attack of migraine. These drugs are rimegepant and ubrogepant and they are expected to be approved by the FDA in about 6 months.

One interesting presentation by N. George and Z. Ahmed from the Cleveland Clinic and other Cleveland hospitals described 8 patients with trigeminal neuralgia (TN) who also suffered from migraines and were given injections of erenumab (Aimovig). Six out of 8 reported good relief of their neuralgia along with migraines. It is possible that the neuralgia pain was part of their migraine, but it may still be worth trying erenumab in patients with TN who do not respond to standard therapies or Botox.

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Omega-3 polyunsaturated fatty acids (PUFA) which are found in fish oil, have been studied in a wide variety of diseases, ranging from Alzheimer’s disease to Herpes Zoster (shingles). Omega-3 PUFA have proven anti-inflammatory and neuroprotective properties and have been used to treat rheumatoid arthritis, Crohn’s disease, ulcerative colitis, psoriasis, lupus erythematosus, multiple sclerosis, as well as migraine headaches.

A new study just published in Neurology showed a strong beneficial effect of Omega-3 PUFA in the treatment of diabetic nerve damage, or diabetic sensorimotor polyneuropathy in patients with type 1 diabetes. After one year of taking 750 mg of EPA and 560 mg of DHA (two of the main omega-3 fatty acids) there was a significant improvement in the nerve function.

Omega-3 PUFA are proven to help patients with coronary artery disease, while in many other conditions, including migraines, the evidence is not as strong. However, considering that we have a very large amount of data showing a benefit in a wide variety of conditions and that Omega-3 PUFA are very safe and inexpensive, it is reasonable to try EPA with DHA for any auto-immune or inflammatory condition, as well as depression.

Eating fatty fish, such as salmon and sardines 2-3 times a week can be sufficient for general health, but those with coronary artery disease and other conditions could benefit from a daily supplement. Also, fish often contains mercury, which can cause neurological and other problems. Omax3 and prescription fish oil, Lovaza are my preferred products because they contain no mercury and are highly concentrated, requiring only 1 or 2 pills a day.

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Trigeminal neuralgia is a rare, but an extremely painful conditions. Patients compare the quality and the severity of pain to an electric shock. The underlying cause is usually compression of the trigeminal nerve by a blood vessel inside the skull and underneath the brain. Surgery to place a teflon pad between the nerve and the blood vessel is curative, but many patients can avoid surgery by using drugs such as carbamazepine, oxcarbazepine, baclofen, and other. Botox, which is approved only for one pain condition – chronic migraines, appears to help other painful conditions, including trigeminal neuralgia (TN). A single previous double-blind placebo-controlled study by Chinese doctors confirmed our clinical observation that Botox does indeed help TN.

A new report presented at the annual meeting of the American Headache Society, also by Chinese researchers describes another positive study. This study compared a single injection of Botox with two injections separated by two weeks. It is not clear what was the logic in giving a second treatment so soon after the first one since Botox effect lasts 3 months. They followed 81 patients for 6 months and both groups had more than 80% success in the first 3 months and somewhat less of an effect in the last 3 months of the study. This was not a blinded study, but placebo response is relatively low in TN, probably because of the high pain intensity. While this study was not as scientific as the first one, it does offer some additional evidence of the efficacy of Botox for TN. Botox is certainly much safer than medications, although facial asymmetry can be an unpleasant cosmetic side effect, especially if pain involves the second branch of the TN (middle of the face).

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Several of my patients with trigeminal neuralgia (TN) responded to Botox injection (although some have not). My previous post on this topic four years ago discussed a study involving 40 patients with TN, of whom 68% responded to Botox. Recently, two new cases of TN successfully treated with Botox have been reported and in the past month I’ve treated three additional patients. Two of my patients had excellent relief and one had none.

One of the case reports was presented at the recent meeting of the American Headache Society in San Diego. This was a 65-year-old woman who suffered from very severe electric shock-like pain typical of TN. She did not respond to a variety of medications, including carbamazepine (Tegretol), but did respond to Botox injections. Botox did not eliminate her pain, but the severity of it was reduced by 50% and this significantly improved the quality of her life.

The current issue of Headache contains a report of a 60-year-old man with severe TN who also did not respond to any medications. He did obtain complete relief from Botox injections and Botox has remained effective for over 2 years.

With any new treatment we usually hope to see large double-blind controlled clinical trials and eventually an FDA approval. FDA approval usually compels insurance companies pay for the treatment. Botox injections have received approval for chronic migraines, excessive sweating, twitching of muscles around the eyes (blepharospasm), and several other conditions. Unfortunately, it is not likely that Botox will receive approval for the treatment of TN because it is a relatively rare condition, which will make it difficult to conduct a large blinded trial. Fortunately, the amount of Botox needed to treat TN is much smaller than what is used for migraines, making a little more affordable. We use 100 to 200 units of Botox for chronic migraines (the FDA-approved protocol calls for 155 units injected over 31 sites) and only 20 to 50 units for TN.

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A patient of mine just emailed me about a recent segment of the TV show, The Doctors, which featured a woman whose severe chronic migraines were cured by nasal surgery. The segment was shot a few weeks after the surgery, so it is not clear how long the relief will last in her case. The surgery involved removing a contact point, which occurs in people with a deviated septum. The septum, which consists of a cartilage in the front and bone in the back, divides the left and the right sides of the nose. If the bony septum is very deviated, which often happens from an injury, it sometimes touches the side of the nose, creating a contact point between the septum and the bony side wall of the nose.
contact point headache
Several small reports by ENT surgeons have described dramatic relief of migraine headaches with the removal of the contact point. If headaches are constant, then the constant pressure of the contact point would explain the pain. However, many of the successfully treated migraine sufferers had intermittent attacks. The theory of how a contact point could cause intermittent migraines is that if something causes swelling of the mucosa (lining) of the nasal cavity, then this swelling increases the pressure at the contact point and triggers a headache. This swelling can be caused by nasal congestion due to allergies, red wine, exercise, and possibly other typical migraine triggers.

This is a good theory, but it is only a theory and the dramatic relief seen after surgery could be all due to the placebo effect. The only way to prove that contact point headaches exist and can be relieved by surgery is by conducting a double-blind study, where half of the patients undergoes surgery and the other half does not. Giving both groups sedation and bringing them to the operating room will blind the patient while the neurologist who evaluates them will also not know who was operated on and who was not, making this a double-blind study. This design is also good only in theory because those who had surgery will have bloody nasal discharge and nasal packing, thus breaking the blind.

However, despite the fact that we will not see any double-blind studies in the near future, there is one way to predict who may respond to contact point surgery. An ENT surgeon can spray a local anesthetic, such as lidocaine, around the contact point during a migraine attack and if pain goes away, then surgery is more likely to help. I would not recommend anyone having surgery without such a test.

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