Cluster Headache Jan 2022 Flashcards
What is an alternate name for Cluster Headache? trigeminal autonomic cephalgia.
Common or Rare? Rare, <1% of population.
Age of onset: 30 years
Male:Female ration? 2-3:1
Symptoms? severe unilateral pain located in the orbital, supraorbital, and/or temporal region that occur from every other day up to eight times per day and last from 15 to 180 minutes
Associated SS? ipsilateral autonomic symptoms (most commonly lacrimation, conjunctival injection, nasal congestion or rhinorrhea, ptosis, edema of the eyelid, sweating of the forehead or face, and miosis) and a sense of agitation or restlessness.
Attacks occur in clusters, called bouts, and are episodic or chronic.
Triggers? include alcohol, nitroglycerin, food containing nitrates, and strong odors
Treatment, abortive? triptans and oxygen; transitional treatments include steroids and sub-occipital steroid injections;
Treatments, prophylactic? verapamil, lithium, melatonin, and topiramate.
Newer treatments? galcanezumab, neurostimulation, and somatostatin receptor agonists.
Cluster headache, the most common form of trigeminal autonomic cephalgia, is a rare primary headache disorder that affects less than 1% of the population. The mean age of onset is 30 years, and it is two to three times more common in males. Cluster headache consists of attacks of severe unilateral pain located in the orbital, supraorbital, and/or temporal region that occur from every other day up to eight times per day and last from 15 to 180 minutes. The pain is associated with ipsilateral autonomic symptoms (most commonly lacrimation, conjunctival injection, nasal congestion or rhinorrhea, ptosis, edema of the eyelid, sweating of the forehead or face, and miosis) and a sense of agitation or restlessness. Attacks occur in clusters, called bouts, and are episodic or chronic. Common triggers include alcohol, nitroglycerin, food containing nitrates, and strong odors. Abortive treatments include triptans and oxygen; transitional treatments include steroids and suboccipital steroid injections; and prophylactic treatments include verapamil, lithium, melatonin, and topiramate. Newer treatments for cluster headache include galcanezumab, neurostimulation, and somatostatin receptor agonists.
Key Reccomendatioins
- A sense of restlessness is one key feature of cluster headache and should be elicited in the history.
- First-line abortive therapies for cluster headache include 100% supplemental oxygen, subcutaneous sumatriptan (Imitrex), sumatriptan nasal spray, and intranasal zolmitriptan (Zomig).
- Suboccipital steroid injection may be considered for transitional therapy to provide time for prophylactic therapy to take full effect.
- First-line prophylactic therapy for cluster headache is verapamil.
Epidemiology of Cluster Headaches
Typical age of onset is 20 to 40 years; it is two to three times more common in men than women.
Lifetime prevalence is 124 per 100,000.
Having a first-degree relative with cluster headache increases the patient’s risk five to 18 times, whereas having a second-degree relative with cluster headache increases the risk one to three times.
Diagnosis
Cluster headache is a clinical diagnosis based on the criteria described in Table 1.
Cluster headache patterns are episodic or chronic. Headache episodes that last seven days to one year with remission periods lasting three months or longer are episodic. When episodes last for one year or longer with remission periods of less than three months, they are categorized as chronic.
A suggested approach to the evaluation of acute headache is summarized in Figure 1.
Symptoms: Table 1
Associated symptoms
At least one ipsilateral symptom in the eye, nose, or face; restlessness or agitation
Duration
15 to 180 minutes*
Frequency
One episode, at least every other day, up to eight episodes per day*
Location
Unilateral orbital, suborbital, and/or temporal
Pain quality
Severe or very severe pain*
Note: At least five episodes are required for a diagnosis. Symptoms cannot be attributed to another condition.
Algorithm: Figure 1
Differential Dx
The differential diagnosis of cluster headache includes other trigeminal autonomic cephalgias such as paroxysmal hemicrania, short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing, short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms, hemicrania continua, or secondary cluster headache caused by intracranial structural lesions (e.g., pituitary adenoma).1,7
Trigeminal neuralgia typically affects the second and third branches of the trigeminal nerve, whereas the first branch is affected in cluster headache.1,7
Migraine headaches are often accompanied by other symptoms that are not typical of cluster headache, including photophobia, phonophobia, and nausea or vomiting. Most patients with migraine find movement worsens their headache, whereas patients with cluster headache can feel agitated and restless.
History and Physical
The typical presentation of cluster headache is unilateral severe pain in the orbital, supraorbital, and/or temporal region and is associated with one or more ipsilateral autonomic symptoms, including conjunctival injection, lacrimation, rhinorrhea, nasal congestion, miosis and/or ptosis, eyelid edema, and facial sweating. Another key symptom is a sense of restlessness.
A cluster headache can last from 15 to 180 minutes when untreated and occurs up to eight times per day in a long-term pattern.
Triggers include medications (vasodilators) such as nitroglycerin, histamine release, tobacco exposure, alcohol, foods that contain nitrates, nail varnish, and petroleum.
Diagnostic testing
Neuroimaging with computed tomography or magnetic resonance imaging is not routinely recommended.
Imaging should be performed in patients with sudden changes in headache features (e.g., sudden onset, frequency, severity, location, worst headache of the patient’s life), presence of neurologic findings (e.g., double vision, blindness, weakness, change in mental status or personality), or systemic illness (e.g., fever, rash).
Treatment
Treatment consists of abortive therapy for acute attacks, transitional therapy to provide temporary relief until prophylactic therapy takes effect, and prophylactic therapy for the duration of the episodic cluster or long-term management of chronic cluster headache.
Abortive Therapy
First-line therapies include triptan drugs and 100% oxygen.19
Subcutaneous sumatriptan (Imitrex), 6 mg, is a first-line treatment option. In two randomized placebo-controlled trials, sumatriptan provided relief as early as 15 minutes after being administered (74% decrease in headache severity in the sumatriptan group vs. 26% in the placebo group).2,8,20–22
Sumatriptan nasal spray, 20 mg, is considered a first-line option for acute bouts of cluster headache, although it acts slower than subcutaneous sumatriptan.28
Oral zolmitriptan (Zomig) is considered a second-line treatment option. It is effective only for acute attacks in episodic cluster headache.2,8,23
Zolmitriptan nasal spray, 5 mg or 10 mg, reduces headache severity at 30 minutes compared with placebo (number needed to treat [NNT] = 2 to 3 for 10 mg; NNT = 5 to 6 for 5 mg) and is considered a first-line therapeutic option.2,24,25
Adverse effects of triptans include paresthesia; heaviness felt in limbs, chest, head or neck, and other parts of the body; asthenia; nausea; and dizziness.8,23
Triptans are contraindicated in patients with cardiovascular disease, cerebrovascular disease, and uncontrolled hypertension.12
100% oxygen is considered first-line therapy for acute cluster headache. One randomized controlled trial found it effective at a flow rate of 12 L per minute for 15 minutes (NNT = 2).16,26
The U.S. Centers for Medicare and Medicaid Services does not cover home oxygen for cluster headache, but many private health care insurance providers reimburse the cost of oxygen use for this indication.9,27
Octreotide (Sandostatin), 100 mcg per mL administered subcutaneously, was shown to be superior to placebo (52% decrease in headache severity in the treatment group vs. 36% in the placebo group; NNT = 7) in one double-blind placebo-controlled crossover study. Gastrointestinal upset was the most common adverse effect. Octreotide is not contraindicated in patients with ischemic heart disease.13
Nasal lidocaine may be considered for treatment of acute cluster headache.8,11 In a small randomized crossover trial with 15 patients, 1 mL of 10% lidocaine administered nasally via a cotton swab to the area corresponding to the sphenopalatine fossa resulted in a shorter time to headache extinction compared with saline application (37 vs. 59 minutes; P < .05).11
Although intramuscular ergotamine, dihydroergotamine nasal spray, intravenous somatostatin receptor agonists, and oral prednisone have been shown to improve cluster headache response, one systematic review and meta-analysis concluded that there is insufficient evidence to recommend their use because of methodologic limitations of the studies.8 In a double-blind placebo-controlled trial, dihydroergotamine nasal spray reduced cluster headache severity compared with placebo (29.9% vs. 9%; NNT = 5).
Transitional Therapy
Transitional therapy, such as suboccipital steroid injections and oral or intravenous corticosteroids, should be considered during initiation of prophylactic therapy to provide time for the prophylactic therapy to take full effect.12,14,30,31
First-line transitional therapy is suboccipital steroid injection.32,33
Only short-term use of corticosteroids is recommended because of serious adverse effects associated with their use.
Prophylactic Therapy
Verapamil is considered the first-line agent for cluster headache prophylaxis.2,12 A double-blind, parallel-group, randomized controlled trial comparing verapamil, 120 mg three times per day, with placebo found that those given verapamil were more likely to have a decrease of headache frequency by at least one-half (80% vs. 0%).37 Most experts agree that electrocardiography should be performed before beginning verapamil therapy, but there is no consensus on whether monitoring with electrocardiography should be done with dose changes.34
My note: Arrhythmias 19% and Bradycardia 36%.
Galcanezumab (Emgality) is a monoclonal antibody targeting calcitonin gene–related peptide and is approved by the U.S. Food and Drug Administration for treatment of migraine. It was shown in a randomized trial to decrease headache frequency by at least one-half more often than with placebo during weeks 1 through 3 (71% vs. 53%; P < .05; NNT = 5).35 In that study, it was administered subcutaneously once per month as three consecutive injections with a pre-filled syringe of 100 mg per mL. The long-term safety and durability of the drug’s benefit require longer studies.14
Nasal civamide, 50 mcg, may be modestly effective as prophylaxis for episodic cluster headache, but it is not available in the United States.18,38
Melatonin, 10 mg per day, may be considered for prevention of cluster headache, particularly in patients who are not able to tolerate other medications.8,19,39,40
Lithium may be considered if verapamil is contraindicated or not effective.12,42
Although topiramate (Topamax) has been recommended, there is no evidence from clinical trials.12,14
Valproate sodium does not appear to be an effective treatment option for cluster headache.8,14,39,43
Verapamil: Warnings/Precautions
Disease-related concerns:
- Accessory pathway (eg, Wolff-Parkinson-White syndrome): During an episode of atrial fibrillation or flutter in patients with an accessory pathway or preexcitation syndrome, use has been associated with increased anterograde conduction down the accessory pathway leading to ventricular fibrillation; avoid use in such patients (ACLS [Neumar 2010]; AHA/ACC/HRS [January 2014]).
- Arrhythmia: Considered contraindicated in patients with wide complex tachycardias unless known to be supraventricular in origin; severe hypotension likely to occur upon administration (AHA [Panchal 2020]).
- Attenuated neuromuscular transmission: Decreased neuromuscular transmission has been reported; use with caution in patients with attenuated neuromuscular transmission (Duchenne muscular dystrophy, myasthenia gravis); dosage reduction may be required.
- Hepatic impairment: Use with caution in patients with hepatic impairment; dosage reduction may be required; monitor hemodynamics and possibly ECG in severe impairment. Avoid repeated injections of IV verapamil in patients with significant hepatic failure.
- Increased intracranial pressure: IV verapamil has increased intracranial pressure in patients with supratentorial tumors at the time of anesthesia induction; use with caution in these patients.
- Left ventricular dysfunction: Avoid use in patients with heart failure due to lack of benefit and/or worse outcomes with calcium channel blockers in general (ACCF/AHA [Yancy 2013]; AHA [Panchal 2020]).
- Renal impairment: Use with caution in patients with renal impairment; monitor hemodynamics and possibly ECG in severe impairment.
See above
Surgical treatment
There are several invasive neurostimulation devices intended for the treatment of cluster headache.
In two randomized controlled trials, sphenopalatine ganglion stimulation decreased the frequency of chronic cluster headache attacks and provided acute relief.<u>18</u>,<u>44</u> In one study, 67.1% of patients who received treatment with sphenopalatine ganglion stimulation achieved pain relief in 15 minutes compared with 7.4% in the sham treatment group (NNT = 2; P < .0001).<u>44</u> Further research is needed to establish its role in clinical practice.<u>18</u>
There is insufficient evidence of benefit to recommend deep brain stimulation.<u>45</u>,<u>46</u>
Gamma Knife radiotherapy was studied in a prospective, nonblinded, open study, but the morbidity was too great for the low rate of pain cessation even in patients with refractory chronic cluster headache.<u>48</u> In a more recent case series, Gamma Knife radiotherapy decreased cluster headache pain significantly in 60% of treated patients at 34 months’ follow-up, but 50% of patients who were irradiated at the trigeminal nerve experienced facial sensory dysfunction.<u>49</u>
