Pearls & Oy-sters: Trigeminal autonomic cephalalgias

Pearl.

All cluster headaches need to be treated with abortive, transitional, and preventive therapies.

Oy-ster.

The average time it takes for a patient with CH to be correctly diagnosed is 6.6 years. The average number of physicians seen prior to correct diagnosis is 4, and the average number of incorrect diagnoses prior to a diagnosis of CH is also 4.²

CH has a very typical clinical presentation and for this reason, the aforementioned “oy-ster” is unacceptable as patients suffer needlessly. Cluster sufferers will attest to thoughts of suicide, as the pain is extremely severe, and CH is often dubbed a “suicide headache.”

CH comes in 2 epidemiologic forms. Episodic cluster, the more common form, is characterized by attacks that occur daily during a cluster period, the period of attacks generally lasting 1–3 months, and followed by months or even years of remission before recurring. In chronic cluster, attacks occur for more than 1 year without remission, or with remissions lasting less than 1 month.¹

Attacks are strictly unilateral with associated ipsilateral cranial autonomic features, and can be discerned from migraine by 2 key factors: 1) attack duration is less than the 4 hour minimum duration of a migraine attack according to ICHD-II criteria (CH attacks last 15–180 minutes); and 2) restlessness is present in CH attacks. Migraine attacks are accompanied by avoidance of movement; CH attacks by pacing and other manifestations of agitation.

When an attack of CH or another TAC occurs, the posterior hypothalamus is activated, causing a disruption in the connections for sleep. Thus, CH attacks frequently wake patients out of sleep.³ Finally, the clinician should not be distracted by migrainous symptoms—photophobia can occur in 91% and phonophobia in 89% of CH attacks, and nausea occurs frequently in cluster as well.⁴

All CH sufferers need more than one acute treatment for attacks in case one fails. Because of the abruptness of the attack and its severity, as well as the short duration, oral medications should be avoided— they are too slow.

An extremely effective treatment to terminate a cluster attack is 6 mg of subcutaneous sumatriptan, achieving relief in 74% of patients within 15 minutes of onset vs placebo, and this formulation and dosage is Food and Drug Administration–approved for cluster.⁵ Sumatriptan nasal spray at 20 mg has also been shown to be effective in randomized controlled trials, and 5 mg zolmitriptan nasal spray has also demonstrated efficacy vs placebo.⁵

All patients should be given a portable 100% oxygen tank for acute treatment, and O₂ becomes the first line therapy if triptans are contraindicated. A non-rebreather mask is used at a flow rate of 7–15 L for 20 minutes and can be repeated safely without issue.⁵ Other effective abortive treatments include IV, IM, or subcutaneous dihydroergotamine, possibly intranasal lidocaine, and blockade of the ipsilateral greater occipital nerve.^2,5

Many patients will present with a sense that a cluster cycle or period is beginning, and will know when attacks are starting. This is an excellent time to begin prophylactic therapy, which should be increased quickly but carefully until the majority of attacks have ceased. Otherwise, prevention is added as soon as the patient notes the cluster period has begun. Prevention might not be needed if at the end of a cycle.

The mainstay of preventive therapy is verapamil. It is typically tolerated up to 480 mg a day, although higher doses can be necessary. Patients can experience constipation, palpitations, peripheral edema, hypotension, and bradycardia. It is recommended that patients have an EKG with each significant increase in dosage.⁶

Because verapamil has significant side effects at higher doses, and because tachyphylaxis tends to occur with monotherapy, many headache specialists use a second preventive at the initial onset of treatment. Other drugs that can be effective include lithium, divalproex sodium, gabapentin, topiramate, methysergide, and, occasionally, melatonin (for episodic CH), or nasal capsaicin.^7–10

Transitional treatment should be provided on the first visit while preventive medications are initiated, typically for 1–2 weeks. Corticosteroids can be used, beginning with 60–80 mg of prednisone daily and tapered by 20 mg every 3–4 days. Ergotamine tartrate at 2 mg or dihydroergotamine injection at 1 mg daily can be used effectively as well but preclude use of triptans for 24 hours after use.⁵

Pearl.

All patients with suspected PH or SUNCT/SUNA need to have an MRI of the brain with and without gadolinium.

Oy-ster.

Patience with the patient is necessary as multiple medications may need to be tried before finding one that is effective.

PH and SUNCT/SUNA are characterized by multiple daily attacks of unilateral head pain with cranial autonomic features. As with cluster, PH comes in 2 forms: an episodic form, in which attacks occur in periods lasting 1–3 months followed by times of remission and recurrence; and a chronic form without a month of remission during a year. Chronic PH is more common.

Attacks of PH last 2–30 minutes, and occur more than 5 times per day at least half the time. Attacks can be differentiated from CH in that they are shorter, 50% of patients will not experience the restlessness that comes along with CH, and the patients may not be awakened from sleep. PH occurs more often in women; CH in men.

The best diagnostic marker for PH is the excellent response to indomethacin. We typically begin 25 mg of indomethacin 3 times a day and increase every 2–3 days until 75 mg TID is reached (if needed). This should be tapered every so often to see if remission has occurred, as the natural progression of PH is largely unknown.⁷ Other medications reported with occasional success include verapamil, celecoxib, acetazolamide, lithium, oxygen, ergotamine, and prednisone.¹¹

SUNCT/SUNA is similar to PH but attacks last only 5–240 seconds (average 10–60 seconds) with up to 200 attacks per day.

Whereas CH, PH, and hemicrania continua (HC) occasionally occur without autonomic symptoms, SUNCT/SUNA attacks are defined by these features.¹¹ SUNCT/SUNA can be differentiated from trigeminal neuralgia (TN) by the V₁ distribution (<10% of TN), the absence of triggers, the higher frequency of attacks per day, and the presence of autonomic symptoms.¹¹

SUNCT and SUNA may be refractory to treatment. Because the attacks are so short, therapy must be preventive. Lamotrigine (especially for SUNCT) and gabapentin (especially for SUNA) are the 2 most efficacious medications reported, but topiramate, intranasal lidocaine, corticosteroids, and IV phenytoin have been used as well.¹²

Imaging of the brain is required when suspecting PH or SUNCT/SUNA, as there are secondary causes that when treated, may resolve these conditions. Reported MRI findings of cerebellopontine angle tumors, prolactinomas, meningiomas, venous angiomas in the brainstem, lacrimal gland retention cysts, and brainstem infarctions have all been described as causing secondary TACS, with pituitary tumor resection occasionally associated with cure.¹¹

Pearl.

Hemicrania continua is a unilateral headache with similar autonomic symptoms but is constant and responds well to indomethacin.

Oy-ster.

Cervicogenic headache can be a mimicker of HC, particularly in the elderly.

HC is a continuous, unilateral, moderate level side-locked headache with severe exacerbations of variable duration manifesting at least one ipsilateral cranial autonomic symptom. HC is probably much more common than originally thought and often misdiagnosed.²

HC can also be accompanied by idiopathic stabbing headache, often called “jabs and jolts,” and is frequently associated with an ipsilateral foreign body sensation in the eye, like an eyelash or grit.^13,14 MRIs of the brain are mandatory during the workup, as secondary HC has been reported, often with etiologies similar to secondary PH and SUNCT/SUNA.

Response to indomethacin is a diagnostic marker in HC, as with PH.¹⁵ Other medications occasionally reported as successful include other nonsteroidal anti-inflammatory drugs, gabapentin, lamotrigine, corticosteroids, dihydroergotamine, lithium, and melatonin.¹¹

Cervicogenic headache can mimic almost any headache, especially a TAC, and should be considered when there is lack of response to treatment. Unilaterality of pain, radiation from the neck, and failure to meet ICHD-II criteria for primary headaches can suggest cervicogenic headache as an alternative diagnosis to a TAC. Occipital nerve blocks can be helpful in cervicogenic headache, with physical therapy for maintenance, although Sjaastad et al. suggested controlled C2–3 blocks for diagnosis.¹⁶