Heavy! The first "Guidelines for the Diagnosis and Treatment of Cluster Headache in China" was released, and the key points of diagnosis and treatment were at a glance!

Cluster headache is prone to disability due to the severe pain at the time of its attack, and the current diagnosis accuracy rate in China is low and the treatment is not standardized
.
In order to improve the standardized diagnosis and treatment level of cluster headache in China and benefit more patients with cluster headache, the Neurology Physicians Branch of the Chinese Medical Doctor Association and the Special Committee on Headache and Sensory Disorders of the Chinese Research Hospital Association evaluated the clinical practice of cluster headache at home and abroad and high-quality literature evidence in recent years, and elaborated
on the pathogenesis, clinical manifestations, diagnosis, differential diagnosis and treatment of cluster headache.
Come and study together~

pathogenesis

The pathogenesis of CH is still not fully understood, but it is believed to be mainly due to the synchronous abnormal activity
of three important components of the trigeminal neurovascular pathway, trigeminal nerve-autonomic reflex, and hypothalamus.

Clinical features

CH is mainly divided into episodic CH (eCH) and chronic CH (cCH
).

(1) Time characteristics

CH seizures often have a certain seasonal rhythm, which is easy to occur when the seasons change, such as more in spring and autumn and less in winter
.
At the same time, CH seizures have circadian characteristics, and most patients have a relatively fixed time of daily headache attacks, so they are called
"alarm clock headaches".

(2) Seizure characteristics

1.
Inducements

During the cluster period, alcohol consumption, weather changes, odor stimuli, emotional factors, mental stress, lack of sleep, and drugs (histamine, nitroglycerin) can all induce seizures, the most common triggers being alcohol consumption, weather changes, and lack of
sleep.

2.
Pre-onset (prodromal) symptoms

Prodromal symptoms such as headache-side discomfort and cranial autonomic symptoms (most commonly head and face discomfort, neck stiffness, anxiety, depression, photophobia, etc.
)
may occur 10 to 20 minutes before the CH attack.

3.
Aura symptoms

Threatening symptoms are occasionally seen in CH, where visual aura is the most common type in patients with CH
.

4.
Headache features

CH presents as severe or very severe pain in the orbit, supraorbital, and/or temporal regions of the epistylized unilateral episode, which can ripple to the forehead, top, pillow, or face when the pain is severe, and is often characterized by sharp, pulsatidous pain, squeezing pain, or blast pain, which can suddenly stop
.

Constant fixation of the site of headache on one side is an important feature (the frequency of right-hand pain is higher in Asian populations), but some patients also experience a shift in headache lateral changes
between or within different cluster phases.

Headache with ipsilateral autonomic symptoms is an important feature of CH, and more than 90% of patients with CH have at least one of the following symptoms: conjunctival congestion, lacrimation, nasal congestion, runny nose, eyelid puffiness, ptosis, microscopic pupils, facial sweating, and flushing
.

(3) Comorbidities

Patients with CH are often accompanied by depression, sleep disturbances and other brain dysfunction disorders
.

Diagnosis and differential diagnosis

(1) Diagnosis

➤The diagnostic criteria for CH in ICHD-3 are as follows:

1.
Meet 2 to 4 seizures more than 5 times;

2.
Severe or very severe pain that occurs in the unilateral orbit, supraorbital and/or temporal region, if the pain lasts for 15 to 180 minutes without treatment;

3.
At least 1 of the following 2 items are met at the time of headache attack:

(1) At least 1 of the following symptoms or signs (and ipsilateral headache): (1) conjunctival hyperemia and/or lacrimation; (2) nasal congestion and/or runny nose; (3) Eyelid edema; (4) Sweating of the forehead and face; (5) Miasis of the pupil and / or ptosis; (2) irritability or restlessness;

4.
The frequency of seizures is 1 time every other day to 8 times a day;

5.
Cannot be better explained
with other diagnoses in ICHD-3.

➤ Episodic CH: The cluster phase lasts 7 days to 1 year, and the headache remission period lasts at least 3 months
.

Diagnostic criteria: (1) The seizure meets the diagnostic criteria of CH and occurs during the cluster phase; (2) At least 2 cluster stages last from 7 days to 1 year (untreated), and the headache remission period ≥ 3 months
.

➤ Chronic CH: Headache in the cluster phase has no remission period of at least 1 year or the remission period is less than 3 months
.

Diagnostic criteria: (1) The seizure meets the CH diagnostic criteria and meets the criteria (2); (2) There is no remission period within at least 1 year or the remission period is less than 3 months
.

(2) Differential diagnosis

The diagnosis of CH should first exclude secondary causes and differentiate them from other trigeminal autonomic headaches, such as paroxysmal migraine, transient unilateral neuralgia-like headache attacks with conjunctival congestion and lacrimation, and distinguish primary headaches such as migraine and sleep headache with ipsilateral autonomic symptoms
.
The CH diagnosis and treatment flow chart is shown in Figure 1
.

Figure 1 CH treatment flowchart

1.
Secondary headache: some of the structural damage of the skull can be similar to CH, and the symptoms alone often cannot distinguish it, and comprehensive diagnostic evaluation
is required.

2.
Other trigeminal autonomic headaches: most of the CH attacks are accompanied by trigeminal autonomic symptoms, so it is necessary to further distinguish with paroxysmal migraine, persistent migraine, SUNCT, etc.
according to the characteristics of headache, such as the duration, frequency and treatment response to indomethacin
.
The duration of different types of headaches may overlap, so clinical analysis
in conjunction with other features is required.
The main clinical features of CH and other trigeminal autonomic headaches are shown in Table 1
.

Table 1 The main clinical features of CH and other trigeminal autonomic headaches

3.
Other primary headaches:

(1) Migraine: There may sometimes be a certain phenotypic overlap between migraine and CH, which can easily lead to misdiagnosis
.
If the migraine attack is strictly unilateral, or coexists with ipsilateral cranial autonomic symptoms, or if the cluster headache attack has a lateral switch of headache, aura symptoms, accompanied by photophobia, nausea, or vomiting, the two should be carefully distinguished
.

This headache is more supportive of migraine when the following conditions occur: (1) In the case of untreated, the headache lasts longer; (2) Daily physical activity will aggravate the headache or avoid daily activities due to headache (clinically, many migraine patients choose to stay in bed instead of continuing to move or work during the headache attack, on the contrary, CH patients are often restless during the headache attack); (3) The severity of pain is different, migraine is often moderate or severe pain, and CH is often very severe pain
.
But when there are obvious periodic regularities, headaches are more supportive of CH
.

(2) Sleep headache: sleep headache only occurs during sleep, mostly between 1:00 and 3:00 in the morning, so it can occasionally be confused
with CH.
Sleep headache attacks are often more frequent, up to 10 times a month, lasting more than 3 months, often leading to patients waking up during sleep, headaches lasting more than 15 minutes after waking up, can be as long as 4 hours; Usually presents with mild or moderate pain, with severe headache
in one fifth of patients.
The difference between it and CH is that the former has a predominant female patient, with a female-to-male ratio of 1.
7:1; the age of onset is older, often after the age of 50; Pain is more bilateral than unilateral; Symptoms of lack of autonomic nerves; And sleep headache occurs during strict sleep, and CH can also occur during the day; In terms of treatment, the similarity with CH is that sleep headache is also effective for lithium carbonate treatment, but sleep headache may be effective when taking caffeine, indomethacin, and flucquarizine hydrochloride before bedtime, which is different from CH
.

treat

The treatment of CH is divided into three types: acute treatment, preventive treatment and transitional treatment, and in recent years, some new drugs and neuromodulatory technologies have also been gradually used in the treatment of CH
.

(1) Acute phase treatment

1.
Treatment objectives: to quickly relieve headache, as soon as possible to terminate the acute stage of headache attacks
.

2.
Commonly used criteria for evaluating the effectiveness of treatment: (1) painless within 15 minutes; (2) The degree of headache within 30 minutes (from moderate or very severe pain to mild or no pain); (3) The duration of pain improvement is up to 60 minutes; (4) There is no need to take the drug
again within 15 minutes of treatment.

3.
Recommendation and evaluation of acute treatment (see Table 2).

Table 2 Recommended treatment of acute CH attacks in adults

(2) Preventive treatment

1.
Purpose of treatment: The purpose of preventive treatment is to reduce the frequency of headache attacks in the cluster period, reduce the degree of seizures, and improve the efficacy
of acute treatment.

2.
Indicators of the effectiveness of preventive treatment: (1) the frequency of headache attacks during the cluster period is reduced; (2) The duration of headache decreases; (3) The degree of headache is reduced and the response to acute treatment is improved
.

3.
Indications for preventive treatment

Prophylactic treatment should be considered when CH causes the patient to: (1) the patient's quality of life, work, or studies are severely impaired (as judged by the patient himself); (2) Frequent headache attacks during the cluster period; (3) The effect of drug treatment in the acute stage is not good or the patient cannot tolerate it
.

4.
Prophylactic therapeutic drugs

(1) Verapamil: currently considered a first-line treatment drug for preventive treatment of CH
.
Studies have shown that verapamil 360 mg is effective in reducing the daily frequency of attacks, with a maximum therapeutic dose of 960 mg
per day.
Verapamil should be administered 1.
5 times longer than the previous cluster phase, and the best response
can be achieved 2 to 3 weeks after administration.
The incidence of heart block caused by verapamil is relatively high, and an electrocardiogram should be performed before and after dose increase during treatment, and heart rate and blood pressure
should be closely monitored during medication.

(2) Lithium salt: For patients who fail to treat verapamil, cannot obtain verapamil, or cannot use verapamil because of adverse reactions, lithium salt can be used as a second-line drug
for preventive treatment.
However, long-term use can lead to renal insufficiency and hypothyroidism
.

(3) Melatonin: the correlation between the hypothalamus and CH and the circadian rhythm of CH seizures support the feasibility
of melatonin therapy.

(4) Other drugs: the evidence for the preventive treatment of topiramate for CH is not sufficient, and it is only used when verapamil or lithium treatment fails or is not available
.
Common adverse reactions include cognitive impairment, paresthesias, speech disorders, etc.
, and are contraindicated
in patients with kidney stones.
Other agents include warfarin, dimergometrine, and sodium
hydroxybutyrate.

(3) Transitional treatment

1.
Transitional treatment purpose and indications: Since prophylactic treatment drugs take a certain amount of time and drug doses to effectively exert their therapeutic effect, for patients with high-frequency attacks with headache frequency ≥ 2 times a day, transitional treatment can be used when prophylactic drugs are started or the dose is increased, and the treatment cycle usually lasts no more than 2 weeks
.

2.
Indicators of the effectiveness of transitional therapy: (1) frequency of episodes of CH; (2) Duration of headache; (3) The degree of headache; (4) The number of times the drug is used in the acute stage of the attack; (5) Cluster period time
.

3.
Drug evaluation and recommendation of transitional therapy (see Table 3).

Table 3 CH prophylactic and transitional treatment recommendations

(4) Neuromodulation therapy

1.
Purpose of treatment: For refractory CH that does not respond to drug therapy or is intolerant to conventional treatment, non-invasive or invasive neuromodulation therapy can be used to reduce the serious adverse effects of headache on patients and their disability
.

2.
Commonly used neuromodulation treatment methods: (1) sphenopalate ganglion radiofrequency ablation; Sphenopalate ganglion stimulation; (3) Non-invasive vagus nerve stimulation; (4) Invasive occipital nerve stimulation; (5) Deep stimulation of the hypothalamus
.

(5) New therapeutic drugs

Relevant studies have shown that CGRP monoclonal antibody and diethylamine ergonoate have a certain efficacy in the preventive treatment of CH, but more evidence
is needed for long-term efficacy and safety.

prognosis

Long-term outcomes varied in patients with eCH and cCH
.
eCH and cCH can be converted to each other, eCH is usually easy to convert to cCH if the control is poor, and cCH can be converted to eCH
with a better prognosis under the standard management.
Studies have shown that late age of onset, men, and disease course of more than 20 years may be key factors influencing CH prognosis
.

summary

In view of the high disabilityability and high disease burden of CH, it is necessary to form a standardized diagnosis and treatment system based on its pathophysiology and disease characteristics, and improve the quality
of clinical management through diagnosis, differential diagnosis and treatment.
However, since cluster headache is relatively rare, the clinical evidence is still relatively lacking or insufficient, and some of the recommendations are weakly recommended, so clinicians need to make comprehensive judgments
based on the hospital environment and specific patient conditions when using this guideline, such as disease severity, patient willingness to treat, patient response to drugs and disease progression.