Progress in diagnosis and treatment strategies of status migraine!

Migraine is a disabling neurovascular disease, and status migrainosus (SM) is defined as a migraine attack lasting more than 72 hours, and the continuous attack can cause severe disability
.
This severe disability includes the inability to go to school, work, social and family activities, and even the thought of committing suicide, especially in patients who have been diagnosed with SM for more than 5 years

1.
The diagnostic criteria, epidemiology and predisposing factors of migraine status

In the third edition of the International Headache Diagnostic Criteria, the diagnostic criteria of SM are defined as: ①In line with the diagnosis of migraine without aura and migraine with aura, in addition to the duration and pain degree, the previous attack is typical; ②It lasts more than 72 hours, Pain or related symptoms gradually decrease
.

Globally, migraine is considered to be the second most disabling disease, with an incidence of about 12% to 15% in the population
.
Currently, there is a lack of epidemiological data on SM.

The predisposing factors for the onset of SM include mental stress, depression, drug abuse and withdrawal, diet, and changes in estrogen levels
.
Menstruation is an important predisposing factor for SM

2.
The pathogenesis of migraine status

There is no evidence to suggest that the pathophysiology of SM conventional migraine patients distinction of any kind, including vascular pathogenesis of the same doctrine, the doctrine of the nerve, the trigeminal vascular theory and so on
.
According to the trigeminal vascular theory of migraine, the suppression of cortical spreading during the onset of SM can activate the final pathway of pain in migraine patients (trigeminal vascular system), releasing large amounts of substance P (SP), vasoactive intestinal peptide (VIP), and Vasoactive substances such as calcitonin gene-related peptide (CGRP) promote the expansion of cerebral blood vessels and increase the permeability of blood vessel walls, leading to the leakage of a large amount of plasma proteins, causing aseptic inflammation, and then inducing headache attacks and related Autonomic symptoms and emotional changes due to headaches

3.
Differential diagnosis of migraine status

Research by Velickovic et al.
showed that among 12,448 migraine patients, the incidence of SM was 14.
4%
.
The proportion of rehospitalized patients due to ischemic infarction, transient ischemic attack, subarachnoid hemorrhage, and cerebral hemorrhage within 30 days was 2.

Therefore, it is necessary to conduct a rapid and systematic evaluation of the patient based on the content of the differential diagnosis, including whether the patient has focal signs of neurological damage, whether there are signs of intracranial hypertension and meningeal irritation, whether there is evidence of infection, and whether there are related lesions in imaging.
or abnormal
.

4.
Complications of persistent migraine

MRI and PET imaging of the head during SM attacks can reveal reversible angiogenic edema, suggesting that there is an increase in the permeability of the blood-brain barrier.
Of course, the relationship between aquaporin and migraine attacks needs to be confirmed by further studies
.
Severe and persistent headache attacks can cause damage to the corpus callosum, Takotsubo cardiomyopathy, and even cerebellar infarction

5.
Treatment strategies for status of migraine

At present, there is a lack of high-quality evidence-based medical evidence for the treatment of SM, and only some expert experience summaries provide clinical reference
.
The following is a systematic elaboration on the treatment progress of SM in recent years

1.
Principles of treatment

① If there is no special contraindication, fully supplement the fluid lost by the patient;

②In principle, use sudden frustration therapy (using larger doses of drugs to quickly stop the persistence of migraine symptoms, and clinically adopt a multi-drug combination program), non-opioid drugs, and multi-drug combination to control seizures;

③Establish a reasonable expectation of SM treatment in the acute phase
.
The treatment goal of chronic headache patients is to relieve the headache to the state before the acute attack of SM

2.
Treatment precautions

①SM is an emergency and severe disease, and sound and light stimulation are not conducive to stopping the attack.
It should be arranged in a relatively quiet emergency room or intensive care unit for treatment;

②SM is usually accompanied by severe nausea, vomiting, and loss of appetite.
The main route of administration is parenteral administration and intravenous administration;

③Need to monitor the changes in nervous system symptoms/signs, and carry out continuous monitoring of vital signs, pay attention to the identification of the early warning symptoms of secondary headache;

④ Pay attention to patients' self-harm and self-harm event protection
.

3.
Types of drugs and physical therapy to control the onset of migraine

3.
Choice of treatment plan

①Serotonin agents: triptan drugs, serotonin 1B/1D receptor agonists, are IA drugs for the treatment of acute migraine attacks, and are still the first choice in the treatment of SM
.
Sumatriptan, zolmitriptan, and rizatriptan are marketed in China.
For SM patients, subcutaneous injections, nasal sprays, anal suppositories or skin patches can be used parenterally
.
The first use is invalid, but the type, dosage form or dose of the triptan can be adjusted and it may still be effective
.
Ergot drugs (dihydroergotamine or ergotamine tartrate) act on serotonin 1B receptors and can inhibit the release of calcitonin gene-related peptide (CGRP)
.
The advantages are long-lasting action, long half-life, and definite curative effect in the acute phase
.
Due to its adverse reactions such as ergot poisoning, heart valve or pulmonary fibrosis, etc.
, its wide application is limited;

② Magnesium agents such as magnesium sulfate, as a N-methyl-D-aspartic acid (NMDA) receptor antagonist, are quick and effective in relieving acute migraine attacks
.
Due to the good economy and safety of the drug, it is the preferred solution for SM patients with moderate to low intensity headaches;

③ Anti-epileptic drugs: including sodium valproate and levetiracetam, anti-epileptic drugs have a positive effect on both the acute treatment and prevention of migraine
.
Open-label clinical studies have confirmed the therapeutic effect of sodium valproate on SM, especially for patients whose traditional treatment methods (such as non-steroidal anti-inflammatory drugs and dopamine receptor antagonists) have failed;

④ Glucocorticoids: Including dexamethasone and methylprednisolone.
Although glucocorticoids have a long history of treating acute migraine, there are still major controversies in clinical studies, and there is no high-level evidence-based medical evidence to support the efficacy evaluation
.
Therefore, whether to apply hormone therapy to SM patients, more consideration should be given to hormone-related adverse reactions.
For patients with a history of co-infection, diabetes, and tuberculosis, it is not recommended to give priority to hormone therapy;

⑤Non-steroidal anti-inflammatory drugs: Among non-steroidal anti-inflammatory drugs, only intravenous ketorolac and acetaminophen are recommended as first-line drugs for the treatment of acute migraine
.
The use of non-steroidal anti-inflammatory analgesics as cyclooxygenase inhibitors in migraine patients is based on their effects on the activation of the trigeminal nerve-vascular system;

⑥Dopamine receptor antagonists, such as metoclopramide (metoclopramide), diphenhydramine, droperidol, promethazine, chlorpromazine (or hibernation mixture) and other drugs have central dopaminergic antagonism , It has a good auxiliary treatment effect for acute migraine attacks or nausea and vomiting associated with SM, and it is an important part of the first-line treatment plan for SM;

⑦Other treatments: including sphenopalatine ganglion block, occipital nerve block, estrogen replacement therapy, mannitol dehydration treatment, these can be used as an adjuvant treatment plan for SM
.

4.
The choice of drugs should be reasonable

① Carefully ask about the history of headache treatment, especially the treatment response to various drugs, which will help guide the next treatment;

②Carefully review the list of medications and current medications used by the patient to avoid adding illicit drugs or creating potentially dangerous drug combinations (such as benzodiazepines? drugs + opioids, leading to respiratory depression; topiramate + sodium valproate, leading to Hyperammonemia and encephalopathy; triptolide + dihydroergotamine, causing cerebrovascular or coronary vasospasm)
.

③Determine whether the patient has a history of opioid use or abuse;

④With untreated hypertension or history of cardiovascular, cerebrovascular or peripheral vascular disease, vasoconstrictor drugs (triptan, ergot preparations) should be avoided;

⑤It is not recommended to overlap use of triptan and ergotamine within 24 hours;

⑥If the patient has a history of upper gastrointestinal ulcer or recent gastrointestinal bleeding, non-steroidal anti-inflammatory drugs should be avoided;

⑦ If hypotension occurs, consider intravenous fluid replacement before and after taking dopamine receptor antagonists and magnesium sulfate and other drugs to avoid a sharp drop in blood pressure after medication
.

6.
Conclusion

Migraine status is a neurological emergency and severe disease.
It requires rapid systematic evaluation of patients, rapid screening of the cause of secondary headaches; a comprehensive grasp of the patient's headache treatment history, and review of the medications and current medications and curative effects of the patients before treatment ; Adopt frustration therapy, non-opioid drugs, multi-drug combination therapy, mainly by parenteral administration and intravenous administration, to quickly terminate the attack
.
In particular, it is necessary to fully understand the patient's past medical history, and pay attention to the complications and contraindications of the drug
.