Status Migrainosus

Debilitating and unremitting migraine headache which lasts at least 72 hours and has been refractory to typical abortive therapy

Primary Category
Headache & Pain
P-Category
Secondary Category
S-Category

Introduction

  • Debilitating and unremitting migraine headache which lasts at least 72 hours and has been refractory to typical abortive therapy.
  • Status migrainosus is classified as a subclass of migraine-related complications
  • Headache-free intervals of less than 4 hours may occur.
  • Also known as an Intractable Migraine with or without aura.
  • Should be addressed in an urgent care or emergency department.

Epidemiology

  • Migraine is a common disorder that affects up to 12 percent of the general population.
  • Prevalence of migraine is inversely correlated with the level of education and household income in the United States.
  • It is more frequent in women than in men, with attacks occurring in up to 17 percent of women and 6 percent of men each year.
  • Ranked among the ten most disabling conditions.
 

Defining Status Migrainosus

International Classification of Headache Disorders (ICHD), 3rd Ed
Migraine Headache:
  • Unremitting for > 72 hours
  • Pain and/or associated symptoms are debilitating

Pathophysiology and Genetics

  • Exact mechanism is unknown.
  • Possible altered circadian secretion of melatonin, suggesting a role of the pineal gland.
  • Angiographic examination revealed presence of multiple segmental stenoses and dilatations of the cerebral arteries along with evidence of inflammation.
  • Another hypothesis of it’s pathogenesis emphasizes the activation and sensitization of the trigeminovascular system via the involvement of different neuropeptides.
  • A genetic component to migraine is indicated by the fact that approximately 70% of patients have a first-degree relative with a history of migraine.

Etiology and Common Precipitating Factors

  • Emotional stress
  • Depression
  • Medication overuse
  • Anxiety
  • Diet
  • Hormonal factors
  • Multiple non-specific factors
  • Organic sleep disorders
  • Generalized anxiety disorder
  • Post traumatic stress disorder

Diagnostic Criteria

☝️
International Classification of Headache Disorders (ICHD-3) Diagnostic Criteria for Status Migrainosus Criteria A
  • A headache attack fulfilling criteria B and C.
Criteria B
  • Occurring in a patient with:
  • Migraine without aura, i.e. headache that has at least two of the following four characteristics; unilateral location, pulsating quality, moderate or severe pain intensity and aggravation by or causing avoidance of routine physical activity, AND/OR
  • Migraine with aura; aura with both of the following: fully reversible visual, sensory and/or speech/language symptoms and no motor, brainstem or retinal symptoms,
  • and typical of previous attacks except for its duration and severity.
Criteria C
  • Both of the following characteristics:
    • Unremitting for > 72 hours
    • Pain and/or associated symptoms are debilitating
Criteria D
  • Not better accounted by another ICHD-3 diagnosis.
 
Note
  1. Remissions of up to 12 hours due to medication or sleep are accepted.
  1. Milder cases, not meeting criterion C2, are Probable migraine without aura.
 
 

Differential Diagnosis

  • Tension headache
  • Cervical spine disease (greater occipital neuralgia)
  • Acute cervical strain (whiplash)
  • Intracranial mass (subacute headache and worsening)
  • Meningitis
  • Subarachnoid hemorrhage (worst headache ever)
  • Optic neuritis
  • Acute glaucoma
  • Pseudotumor cerebri
  • Carotid artery dissection
  • Temporomandibular joint (TMJ) syndrome
  • Sinusitis
  • Rhinogenic headache ("sinus headache")

Evaluation

  • American Academy of Neurology Practice Parameter
    • Neuroimaging (CT or MRI) recommended in patients with:
      • unexplained abnormal neurologic signs (AAN Grade B),
      • atypical headache features or headaches that do not fill specific diagnostic criteria (AAN Grade C).
    • Neuroimaging is not usually recommended for patients with migraine and normal neurologic exam (AAN Grade B).
    • No recommendations made for presence or absence of neurologic symptoms.
    • Insufficient evidence to support guidelines for EEG.

Treatment and Management

Acute/Emergency Management

  • Emergency treatment for patients with status migrainosus should be aggressive.
  • It includes rest; rehydration and electrolyte replacement; detoxification; round-the-clock parenteral analgesic therapy; symptomatic treatment of nausea, anxiety, insomnia, and withdrawal symptoms; concurrent initiation of prophylactic therapy; and behavioral treatment.

Emergency Treatment

Initial
  • IV fluids, normal saline 2-3 L bolus or 80-100 cc/h for as long as patient is in emergency department
  • IV diphenhydramine 12.5-25 mg
  • IV dopamine receptor antagonist medication (typically use metoclopramide 10 mg or prochlorperazine 10 mg)
  • IV magnesium sulfate 500 mg / 1 g
  • IV ketorolac 30 mg
Advanced
Medications are given in succession separated by 15 to 20 minutes
  • If patient does not improve, other options include IV sodium valproate (500 mg), IV levetiracetam (500 mg), or IV methylprednisolone (200 mg)
  • IV dihydroergotamine 0.5-1.0 mg may be used if patient has not used triptan within 24 hours and no contraindications exist

Choice of Treatment

Non-pharmacological

  • Behavioral methods
    • Biofeedback
      • Monitor body temperature on electromyography.
    • Relaxation Techniques
      • Progressive muscle relaxation
      • Imaginary-based relaxation
    • Reinforcement of maintaining a regular schedule, sleep, diet and exercise.
  • Resting or sleeping in a dark, quiet room should be encouraged.
  • Triggers (skipping meals, dehydration, stress, change in sleep patterns, infections, etc.) should be identified and corrected.

Pharmacological Treatment

First Line

  • Triptans
    • Sumatriptan 6 mg
    • Administered subcutaneously
    • May be repeated if ineffective after 1 hour
  • Ergot alkaloids
    • Dihydroergotamine
    • Administered intramuscularly
    • Requires premedication with Prochlorperazine or Metoclopramide 10 mg intramuscularly
    • May be repeated after 1 to 2 hours if ineffective

Second Line

  • Intravenous Hydration
  • Aspirin and NSAIDs
    • Intravenous Ketorolac
  • Prochlorperazine
    • 25 mg rectal suppository, OR
    • 10 mg intramuscularly, OR
    • 10 mg intravenously
  • Opioids
    • Hydromorphone (2 mg orally or 3 mg per-rectal)
    • Morphine (15-30 mg orally or 30 mg per-rectal)
  • Steroids
    • Prednisone 80 mg, tapered over 4 days (20 mg each day)
    • Dexamethasone 8 mg, tapered over 4 days (2 mg each day)
  • Nerve blocks
    • Occipital and trigeminal nerve blocks (safe in pregnancy)

Figure 1A: No contraindication to DHE and Triptans

 
 
notion image

Figure 1B: Contraindication to DHE and Triptans

notion image
 
Derived From: Dawn A Marcus (2001) Treatment of status migrainosus, Expert Opinion on
Pharmacotherapy, 2:4, 549-555, DOI: 10.1517/14656566.2.4.549

Complications and Prognosis

  • Being headache free upon discharge and having continued pain freedom for at least 48 hours post-discharge is a suggested goal for ED treatment of patients with episodic migraine (known as sustained headache freedom)
  • Most ED trials suggest this only occurs in about 20% to 25% of patients.
  • 30% of patients with migraine report a moderate to severe headache within 1 day after ED discharge, and 50% are functionally disabled by that headache.
  • Predictors of poor post-ED outcomes include severe pain at baseline, presence of nausea, and longer duration of headache.

Further Reading

  • Treating status migrainosus in the emergency setting: what is the best strategy?, Expert Opinion on Pharmacotherapy, DOI: 10.1080/14656566.2018.1516205

Bibliography

  1. Unrecognised challenges of treating status migrainosus: An observational study. (n.d.). PubMed Central (PMC). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7367756/
  1. Treating status migrainosus in the emergency setting: what is the best strategy?, Expert Opinion on Pharmacotherapy, DOI: 10.1080/14656566.2018.1516205
  1. Migraine prevalence. A review of population-based studies. Neurology, 44(6 Suppl 4), S17–S23
  1. Prevalence and burden of migraine in the United States: data from the American Migraine Study II. Headache, 41(7), 646–657. https://doi.org/10.1046/j.1526-4610.2001.041007646.x
  1. Treatment of status migrainosus, Expert Opinion on Pharmacotherapy, 2:4, 549-555, DOI: 10.1517/14656566.2.4.549
  1. Evaluation of Triggers of Status Migrainosus and its impact on morbidity (5479) Neurology Apr 2020, 94 (15 Supplement) 5479
  1. Status Migrainosus: Causative and Therapeutic Aspects and disability.
  1. Reversible MRI abnormalities in a patient with recurrent status migrainosus. doi:10.1111/j.1468-2982.2008.01803.x
  1. A REVIEW ON CLASSIFICATION, PATHOPHYSIOLOGY, DIAGNOSIS, AND PHARMACOTHERAPY OF HEADACHE. Innovare Journal of Medical Sciences. 8. 1-12. 10.22159/ijms.2020.v8i6.37667.
  1. 1.4.1 status migrainosus. (n.d.). ICHD-3. https://ichd-3.org/1-migraine/1-4-complications-of-migraine/1-4-1-status-migrainosus/
  1. Birth and Growth Medical Journal 2019;28(3): 132-140. doi:10.25753/BirthGrowthMJ.v28.i3.15431
  1. Migraine ☆. Reference Module in Neuroscience and Biobehavioral Psychology. doi:10.1016/b978-0-12-809324-5.03097-2
  1. www.neurology.org. Neurology, 55(6), 768-768. https://doi.org/10.1212/wnl.55.6.768
  1. Parenteral dexamethasone for acute severe migraine headache: meta-analysis of randomised controlled trials for preventing recurrence. BMJ 2008;336(7657):1359Y1361.doi:10.1136/bmj.39566.806725.BE.
  1. Subcutaneous sumatriptan for treatment of acute migraine in patients admitted to the emergency department: a multicenter study. Ann Emerg Med 1995;25(4):464Y469. doi:10.1016/ S0196-0644(95)70259-8.
  1. Randomized trial of IV dexamethasone for acute migraine in the emergency department. Neurology 2007;69(22)
  1. Recurrence of primary headache disorders after emergency department discharge: frequency and predictors of poor pain and functional outcomes. Ann Emerg Med 2008;52(6):696Y704. doi:10.1016/ j.annemergmed.2008.01.334.
  1. Treatment of status migrainosus, Expert Opinion on Pharmacotherapy, 2:4, 549-555, DOI: 10.1517/14656566.2.4.549
  1. CONTINUUM (MINNEAP MINN) 2018;24(4, HEADACHE):1092–1107
  1. Emergency department and inpatient management of status migrainosus and intractable headache. Continuum: Lifelong Learning in Neurology, 21(4), 1004-1017
 
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