Hemicrania Continua: Diagnosis and Treatment

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Although most cases of hemicrania continua resolve with indomethacin, some patients may require adjuvant therapies.
Although most cases of hemicrania continua resolve with indomethacin, some patients may require adjuvant therapies.

Hemicrania continua (HC), one of the trigeminal primary headaches, causes intense unilateral pain for several months, as well as autonomic symptoms.1,2 Updated classification of headache type is intended to help clinicians better understand and diagnose this headache syndrome.1 Common brain structures are involved in HC and other types of headache (eg, cluster headache and short-acting neuralgiform headache attacks), resulting in autonomic symptoms and disinhibition of the trigeminal autonomic reflex.1

Diagnosing HC Based on the New Classification

Previously, HC was classified in the “other primary headaches” category, but as it is associated with autonomic symptoms, it is now considered a trigeminal autonomic cephalgia, according to the International Classification of Headache Disorders (ICHD) third edition.1,2 In addition to unilateral headache, HC's autonomic symptoms include ipsilateral facial sweating, nasal congestion, rhinorrhea, tearing, conjunctival injection, eyelid edema, and miosis or ptosis. The new definition of HC also recognizes the relapsing-remitting nature of the attacks.

One of the hallmarks of HC is resolution with either an oral dose or intramuscular injection of the nonsteroidal anti-inflammatory drug (NSAID), indomethacin. In countries where indomethacin is available by injection, the “Indotest” is a 50-mg to 100-mg injection of indomethacin that is used both for diagnosis and treatment of HC. Although pain subsides within 24 hours for most patients treated with indomethacin, some individuals may not respond for as long as 10 days. Experts recommend that indomethacin be co-administered with a gastrointestinal protectant, as it may irritate this system.

The new definition of HC, however, is not without controversy. “The presence of cranial autonomic symptoms was a must before the current ICHD-3 β criteria,” said Sanjay Prakash, MD, professor and head of the neurology department at Sumandeep Vidyapeeth University in Vadodara, Gujarat, India. “Now, it is not a must if exacerbations are associated with agitation. We believe that an alternative should also be given for the indomethacin response to HC in the criteria. There is a need of more accommodating type alternative criteria in the appendix section of ICHD-3 β, as clinical features, therapeutic measures, and many other aspects are still to be determined for HC.”3

When Patients With HC Are Unresponsive to Indomethacin

Although most HC cases resolve with indomethacin, some patients may require adjuvant therapies for adequate pain relief.4 Label warnings for indomethacin state that the drug may be associated with an increased risk for myocardial infarction and stroke in patients with cardiovascular disease.4,5 Long-term use of indomethacin may also be associated with hypertension, gastrointestinal pain, vascular events, and bronchial spasms.4

Indomethacin is one of the cyclooxygenase 1 inhibitors with the highest penetration rate in the blood-brain barrier.1 Indomethacin, but not other NSAIDs (ie, naproxen and ibuprofen), was found to inhibit nitrous oxide-dependent vasodilation.1 Other medications that could be considered for HC include topiramate, lamotrigine, naproxen, lithium, onabotulinumtoxinA, and melatonin.1

“If indomethacin does not show the expected effect, first step would be to rethink the diagnosis, afterward if every other condition is ruled out, start with the prophylactic medications described in the literature to be effective (eg, cyclooxygenase-2, topiramate, gabapentine, verapamil),” advised neurologist Ozan Eren, MD, from the German Center for Vertigo and Balance Disorders in Munich, Germany. “And of course, the use of neuromodulation is a great option, as the side effects are usually negligible.”

Nonpharmacologic Therapies for HC

Borrowing from the migraine armamentarium, some clinicians have leveraged invasive techniques to relieve HC pain, including deep brain stimulation, occipital nerve stimulation, and sphenopalatine ganglion stimulation.4 Transcutaneous vagus nerve stimulation and supraorbital nerve stimulation are among the noninvasive methods that have shown promise in patients with chronic migraine and chronic cluster headaches.4

In a case study of a 58-year-old man with intractable HC pain, noninvasive vagus nerve stimulation was associated with a reduction of the patient's oral medications.4 The patient, who was treated with indomethacin (150 mg/day), had a series of myocardial infarctions, which led to coronary artery stenting. Because of his increased risk for thrombotic events, the patient could no longer take indomethacin and was prescribed several other medications, none of which were effective.4 Among prescription drugs the patient took, opioids were associated with fatigue that rendered him unable to work. The patient then opted to be treated with investigational noninvasive vagus nerve stimulation. The treatment was self-delivered using a hand-held stimulator. The patient was able to reduce his dose of opioid and his pain was reduced.4

“You don't need to have an operation anymore to try a transcutaneous stimulator to see if it provides any benefit,” said Dr Eren. “Of course, insurance companies don't cover the costs, at least not in Germany, but there are different programs offered by the companies to try the stimulators. Thus, you can at least see if it works for you.”

Summary & Clinical Applicability

HC, one of the trigeminal primary headaches, causes intense unilateral pain for ≥3 months. Although most cases of HC resolve with indomethacin, some patients may require adjuvant therapies.

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References

1. Mehta A, Chilakamarri P, Zubair A, Kuruvilla DE. Hemicrania continua: a clinical perspective on diagnosis and management. Curr Neurol Neurosci Rep. 2018;18(12):95.

2. International Headache Society. International Classification of Headache Disorders, 3rd edition. Hemicrania continua. https://www.ichd-3.org/3-trigeminal-autonomic-cephalalgias/3-4-hemicrania-continua/ Accessed November 19, 2018.

3. Prakash S, Adroja B. Hemicrania continua. Ann Indian Acad Neurol. 2018(suppl 1):S23-S30.

4. Eren O, Straube A, Schöberl F, Schankin C. Hemicrania continua: beneficial effect of non-invasive vagus nerve stimulation in a patient with a contraindication for indomethacin. Headache. 2017;57(2):298-301.

5. Indocin [prescribing information]. Whitehouse Station, NJ: Merck & Co., Inc.; 2008.

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