The trigeminal autonomic cephalalgias are a group of headache disorders with prominent autonomic features and a shared pathophysiology.
There are four trigeminal autonomic cephalalgias. Each disorder can be either episodic or chronic. The trigeminal autonomic cephalalgias are uncommon headache disorders. Therefore, there is a high misdiagnosis rate350,351 and few randomised-controlled treatment trials.
The clinical characteristics of the trigeminal autonomic cephalalgias as defined by the International Classification of Headache Disorders are based upon the published cases reports and series apart from cluster headache which has population-based data.
The trigeminal autonomic cephalalgias are:
- Cluster headache
- Paroxysmal hemicrania
- SUNCT/SUNA (Short-lasting neuralgiform attacks with conjunctival injection and tearing/Short-lasting neuralgiform attacks with cranial autonomic features)
- Hemicrania continua
Cluster Headache
Clinical Features
Epidemiology
Cluster headache has a prevalence of about 0.1%
The peak age of onset is between the 3rd and 4th decades
The disorder is four times more common in men
Cluster headache sufferers are often smokers
Clinical Features
The current classification of cluster headache is well validated (http://www.ichd-3.org).
Attacks are characterised by excruciating strictly unilateral and strictly unilateral headache. However, attacks can change side, across different bouts, within the same bout and rarely within an acute attack.
Bilateral pain in cluster headache is rare.
The attacks are accompanied by ipsilateral cranial autonomic features which are primarily parasympathetic and can most commonly include lacrimation, conjunctival injection, rhinorrhoea, nasal congestion, drooping or swelling of the eyelid. The presence of cranial autonomic features in headache does not necessarily indicate cluster headache or another TAC. For example, these features can also occur in migraine.
One of the most distinguishing features during the cluster attack is restlessness. Patients typically walk up and down, or rock to and fro, clutching the affected side, unlike migraineurs who are motion-sensitive and prefer to remain still.
Attack duration is usually between 15 minutes to 3 hours and attack frequency 1-2 a day. Cluster headache can be episodic or chronic. Episodic cluster bouts usually last between 2 weeks and 3 months and most often occur once every 1-2 years. Ten to 20% of sufferers experience chronic cluster headache, which is currently defined as attacks occurring without a remission period, or with remissions lasting < 3 month, for at least 1 year.
Active bouts of cluster headache can be seasonal and at the same time each year. During an active bout, sufferers can experience attacks at set times during the day for weeks or months. The pattern can change or become less predictable.
Cluster attacks often wake patients from sleep, usually about 1.5-2 hours after they have fallen asleep.
Some individuals can exclusively have nocturnal attacks.
In between attacks of pain patients can experience a background dull ache in the same distribution of the cluster attacks. The interparoxysmal pain tends to settle when the cluster bout resolves.
During an active cluster bout some patients can be exquisitely sensitive to alcohol triggering an attack, usually within an hour. The propensity does not occur out of the bout.
Clinically relevant commonalities and differences between migraine and cluster headache include:
- Cluster sufferers can have nausea and vomiting, photophobia and phonophobia
- Up to 25% of migraine sufferers can experience autonomic features during an attack
- Aura can be experienced in up to 23% of cluster headache sufferers (though in practice is rare)
- 20-40% of migraine sufferers experience strictly unilateral headache
- The duration of untreated migraine attacks in adults is invariably longer than 4 hours
- A key feature in cluster headache is restlessness and lack of motion sensitivity, while migraine sufferers prefer to be still
Classification of cluster headache (http://www.ichd-3.org)
CLUSTER HEADACHE DIAGNOSTIC CRITERIA
- Severe/very severe unilateral orbital, supraorbital and/or temporal pain lasting 15–180 minutes (untreated)
- Either or both of the following:
- At least one of the following symptoms or signs, ipsilateral to the headache:
- Conjunctival injection and/or lacrimation
- Nasal congestion and/or rhinorrhoea
- Eyelid oedema
- Forehead and facial sweating
- Forehead and facial flushing
- Sensation of fullness in the ear
- Miosis and/or ptosis
- A sense of restlessness or agitation
- At least one of the following symptoms or signs, ipsilateral to the headache:
- Attack frequency between one every other day up to 8/day for > half the time the disorder is active
EPISODIC CLUSTER HEADACHE
- Attacks fulfilling criteria for Cluster headache and occurring in bouts (cluster periods)
- At least two cluster periods lasting from 7 days to one year (when untreated) and separated by pain-free remission periods of three months
CHRONIC CLUSTER HEADACHE
Attacks fulfilling criteria for Cluster headache and occurring without a remission period, or with remissions lasting < 3 months, for at least 1 year
Acute / Responsive Treatment
Management – Acute
The most effective acute treatment is the sumatriptan 6mg subcutaneous injection with significant relief within 15 minutes.
The maximum limit is two 6mg injections a day.
The treatment is generally well tolerated, without tachyphylaxis.
Patients who have cluster headache rarely develop medication overuse headache.
Patients who also have migraine may develop exacerbation of their migraine disorder whilst using a triptan effectively for their cluster attacks.
High flow oxygen 100% at 7-15 litres/minute for 15-20 minutes, using a non-rebreathable mask, is effective in aborting acute attacks of cluster headache.
There is no limit to the use of high flow oxygen, though obvious cautions around smoking/flames/fire hazards near oxygen need to be considered/addressed. Oxygen is often used together with triptans in patients with multiple attacks.
Recommended Acute Cluster attack treatments
|
Treatment |
Formulation |
Strength |
Maximum Daily Dose |
|
Oxygen |
Inhalation through non-rebreathable mask |
7-15 L/min |
No limit |
|
Sumatriptan |
Subcutaneous injection |
6 mg |
12 mg |
|
Sumatriptan |
Nasal spray |
20 mg |
40 mg |
|
Zolmitriptan |
Nasal spray |
5 mg |
15 mg |
|
Non-invasive vagal nerve stimulation |
Transcutaneous |
As per specialist recommendation |
All acute cluster attack treatments
|
Name |
Formulation |
Strength |
Maximum Daily Dose |
Comment |
|
Lidocaine |
Nasal spray |
4% |
Not specified |
Self –administered using a nasal dropper |
|
Octreotide |
Subcutaneous injection |
100 mcg |
Not specified |
|
|
Oxygen |
Inhalation through non-rebreathable mask |
7-15 L/min |
No limit |
|
|
Sphenopalatine Ganglion Stimulation (SPG) |
Implantable device |
As per specialist recommendation |
|
|
|
Sumatriptan |
Subcutaneous injection |
6 mg |
12 mg |
|
|
Sumatriptan |
Nasal spray |
20 mg |
40 mg |
|
|
Zolmitriptan |
Nasal spray |
5 mg |
15 mg |
|
Prophylactic / Preventive Treatment
Verapamil is an effective preventive treatment in cluster headache.
The doses required to suppress cluster headache attacks can be higher than those used to treat cardiac disorders. Clinically significant cardiac rhythm disturbances can occur and are neither dose nor time dependent. It is possible for patients to develop cardiac conduction abnormalities even after they have been on a stable dose for a long period.
BASH recommends an ECG done at baseline and following each increase in dose. At a stable dose ECG should be done once every six months. Any cardiac rhythm disturbance may require dose reduction or drug withdrawal.
In episodic cluster headache, once control has been achieved, towards the end of the expected bout, the preventive can be slowly withdrawn. If attacks recur the preventive should be re-established.
Oral corticosteroids have been shown to be effective in the prevention of cluster headache attacks.
The response should be seen within 48 hours. Given the high adverse effect profile corticosteroid use is best restricted as a short-term measure in patients with multiple daily attacks, which cannot be treated effectively acutely, whilst an alternative preventive is being introduced.
Suboccipital nerve block (i.e. suboccipital depot steroid and local anaesthetic injection) has shown a significant reduction or resolution of attacks compared to placebo and despite a high placebo response rate.
Recommended preventive treatments for cluster headaches
|
Name |
Start dose |
Titration |
Max daily dose |
Comments |
|
Greater occipital nerve block |
Depot steroid + local anaesthetic |
Not applicable |
Not applicable |
Different formulations of steroid & anaesthetic used* |
|
Verapamil |
80 mg TDS |
Increase 80 mg every 2 weeks |
960 mg |
ECG monitoring recommended |
*There does not seem to be a difference between different local anaesthetics
Paroxysmal Hemicrania
Epidemiology
Population-based data on the prevalence of paroxysmal hemicrania is sparse and has been cited as 0.05% in the 18-65-year age group . Total published cases remain less than 200. There may be a slight female preponderance with ratios ranging between 1.1 to 2.36. Mean age of onset is between the 4th and 5th decades .
Clincial Features
The pain is strictly unilateral with associated ipsilateral autonomic features (http://www.ichd-3.org).
The classification of paroxysmal hemicranias is shown as an appendix.
Attack duration ranges between 2-30 minutes and frequency of attacks is reported up to 50 a day. The mean lies between seven and 13 attacks per day. A greater proportion present with chronic paroxysmal hemicrania. The disorder has an absolute response to indomethacin.
The attacks are shorter and more frequent than in cluster headaches and longer and less frequent than in SUNCT/SUNA. The typical circadian characteristics seen in cluster headache are less prominent in paroxysmal hemicrania. All attacks are spontaneous unlike SUNCT/SUNA, in which attacks are often triggered immediately by various sensory stimuli. The key distinction is the clear therapeutic response to Indomethacin. The main differential diagnoses are shown are shown as an appendix.
Management
There are no RCTs for preventive treatment in paroxysmal hemicranias.
Acute Treatment
The attacks of paroxysmal hemicrania are usually too short to respond to any oral acute treatment. Open label observation suggests that sumatriptan 6mg subcutaneous injection and high flow oxygen are generally not effective .
Preventive Treatment
By definition paroxysmal hemicrania is an indomethacin-responsive disorder.
The effective dose range is between 25-300mg daily dose .
Although most patients show a rapid response to indomethacin, some patients can take up to a week to demonstrate a response to an effective dose. Based upon this BASH recommends indomethacin 25mg PO TDS for 7 days, 50mg TDS 7 days, up to 75mg TDS. We recognise and emphasise the higher dose is above the BNF quoted maximum of 200mg per day, and should only be considered if clinically required, after appropriate counselling with the patient, and with clear criteria for dose reduction.
Dose requirements can change over time and some patients may go into remission.
Therefore, once symptoms are well controlled for a period of time gradual dose reduction should be tried to maintain the lowest effective dose or, if there is no recurrence on each dose reduction, withdrawal during remission periods. Gastrointestinal side effects with indomethacin are common and may preclude use of the drug. A concomitant proton-pump blocker or H2-antagonist can be used.
SUNCT & SUNA
The original description of this disorder was termed SUNCT, short-lasting unilateral neuralgiform attacks with conjunctival injection and tearing.
Conjunctival injection and tearing (lacrimation) are the most common autonomic symptoms in all the TACs.
The terminology SUNA was proposed based on the fact that a number of patients were noted to lack one or both of these symptoms.
The distinction remains within the ICHD classification. From a clinical perspective, management remains the same. The distinction remains within the ICHD classification. BASH recommends this as a research tool and for current clinical purposes will adopt the terminology of SUNA to encompass both groups.
Epidemiology
SUNCT/SUNA is rare.
The mean age of onset is 48 years with a slight male preponderance 1.5.
Clinical Features
The attacks are the shortest and most frequent of all the TACs. Attacks can be either spontaneous or induced by cutaneous triggers. Mean duration is about one minute (range 1-600 seconds) with frequency up to 30 attacks in an hour.
The character of the attacks can vary: attacks can occur in single stabs, a group of stabs or a long attack with a ‘saw-tooth’ pattern of stabs between which the pain does not return to baseline. Other features of TACs may be present, such as agitation. SUNCT/SUNA can be misdiagnosed as Trigeminal Neuralgia. However, the location of the pain, autonomic features, duration of attacks and spontaneity of attacks in SUNCT/SUNA, differentiate between the two (See appendix Table. Differential diagnosis of The Trigeminal Autonomic Cephalalgias).
Management
There are no RCTs for preventive treatment in SUNCT/SUNA.
Acute treatment
Because of the short attack duration there are no effective acute treatments in SUNCT/SUNA
Preventive treatment
The most effective reported treatment is lamotrigine with dose range up to 400 mg. Topiramate may be effective in SUNCT. Carbamazepine and gabapentin may also be effective.
Hemicrania Continua
Epidemiology
Hemicrania continua is an uncommon disorder with estimated prevalence of 0.8-1.5% however it is acknowledged that this is compounded by diagnostic inaccuracy.
The disorder seems to be more common in women. Mean age of onset is between the 3rd and 4th decade.
Clinical Features
Hemicrania continua is characterized by strictly unilateral pain of moderate severity with ipsilateral autonomic features which may be more prominent during exacerbations. Hemicrania continua has both clinical and pathophysiological overlap with migraine.
Thus, although more than half of cases can be restless during the attacks, others experience motion sensitivity. Although the disorder is defined by chronicity it can present in a relapsing and remitting (thus episodic) form.
Management
There are no RCTs for preventive treatment in hemicrania continua.
Acute treatment
Medication overuse can occur in hemicrania continua. Thus, analgesics should be withdrawn prior to assessing response to indomethacin.
Preventive treatment
Hemicrania continua is an indomethacin-sensitive disorder. The effective dose range is between 25-300mg daily dose.
Although most patients show a rapid response to Indomethacin, some patients can take up to a week to demonstrate a response to an effective dose. Based upon this BASH recommends Indomethacin 25mg TDS for 7 days, 50mg TDS 7 days, up to 75mg TDS.
Dose requirements can change over time and some patients may go into remission.
Therefore, once symptoms are well controlled for a period of time gradual dose reduction should be tried to maintain the lowest effective dose or, if there is no recurrence on each dose reduction, withdrawal during remission periods.
Gastrointestinal side effects with Indomethacin are common and may preclude use of the drug. A concomitant proton-pump blocker or H2-antagonist can be used