MCQ Quiz: Etiology and Pathophysiology of Migraine

Understanding the complex etiology and pathophysiology of migraine is essential for pharmacists to effectively manage patients and grasp the rationale behind modern therapeutic strategies. The Patient Care VII: Brain and Behavior curriculum dedicates a specific unit to this topic, moving beyond the concept of a simple headache to explore migraine as a complex neurological disorder. This quiz will test your knowledge on the key players in migraine pathophysiology, including the trigeminovascular system, neuropeptides like CGRP, and the mechanisms behind symptoms like aura and allodynia.

1. The modern understanding of migraine pathophysiology is centered on the activation of which system?

• A. The limbic system
• B. The extrapyramidal system
• C. The trigeminovascular system
• D. The renin-angiotensin system

Answer: C. The trigeminovascular system

2. Which neuropeptide is considered a key player in the pathophysiology of migraine, causing potent vasodilation and transmitting pain signals?

• A. Acetylcholine
• B. Dopamine
• C. Calcitonin Gene-Related Peptide (CGRP)
• D. GABA

Answer: C. Calcitonin Gene-Related Peptide (CGRP)

3. The “aura” experienced by some migraine patients is believed to be caused by what neurological phenomenon?

• A. A seizure originating in the temporal lobe.
• B. A wave of intense vasoconstriction in the occipital lobe.
• C. A slow wave of neuronal and glial depolarization across the cerebral cortex, known as Cortical Spreading Depression (CSD).
• D. A sudden drop in serotonin levels.

Answer: C. A slow wave of neuronal and glial depolarization across the cerebral cortex, known as Cortical Spreading Depression (CSD).

4. The “triptans” (e.g., sumatriptan) are effective for acute migraine treatment because their primary mechanism of action is:

• A. Antagonism of CGRP receptors.
• B. Agonism at serotonin 5-HT1B/1D receptors.
• C. Non-selective inhibition of COX enzymes.
• D. Blockade of voltage-gated sodium channels.

Answer: B. Agonism at serotonin 5-HT1B/1D receptors.

5. Activation of 5-HT1D receptors on trigeminal nerve endings leads to what effect that helps abort a migraine attack?

• A. Increased release of CGRP and Substance P.
• B. Inhibition of the release of CGRP and other pain-transmitting neuropeptides.
• C. Potent vasodilation of cranial blood vessels.
• D. Sensitization of the trigeminal nucleus.

Answer: B. Inhibition of the release of CGRP and other pain-transmitting neuropeptides.

6. The throbbing quality of a migraine headache is thought to be related to:

• A. The firing of motor neurons.
• B. The dilation of cranial blood vessels.
• C. A decrease in intracranial pressure.
• D. The release of endorphins.

Answer: B. The dilation of cranial blood vessels.

7. “Neurogenic inflammation” in migraine pathophysiology refers to:

• A. An infection of the meninges by a virus or bacterium.
• B. The extravasation of plasma proteins and inflammatory mediators from dural blood vessels due to the release of neuropeptides.
• C. An autoimmune attack on the myelin sheath of the trigeminal nerve.
• D. Inflammation caused by a traumatic head injury.

Answer: B. The extravasation of plasma proteins and inflammatory mediators from dural blood vessels due to the release of neuropeptides.

8. The “Etiology and Pathophysiology of Migraine” is a core lecture in which Patient Care course module?

• A. Module 6: Epilepsy
• B. Module 7: Other Neuropsychiatric Disorders
• C. Module 5: Anxiety and Sleep-Wake Disorders
• D. Module 2: Neurodegenerative Disorders

Answer: B. Module 7: Other Neuropsychiatric Disorders

9. The strong familial tendency of migraine suggests a significant role for which etiological factor?

• A. Diet alone
• B. Stress alone
• C. Environmental factors only
• D. Genetics

Answer: D. Genetics

10. Activation of 5-HT1B receptors by a triptan causes what effect on dilated cranial arteries?

• A. Further vasodilation
• B. No effect
• C. Vasoconstriction
• D. Inflammation

Answer: C. Vasoconstriction

11. The development of cutaneous allodynia (the perception of pain from a non-painful stimulus, like brushing hair) during a migraine is a clinical sign of:

• A. Peripheral sensitization of trigeminal neurons.
• B. Central sensitization within the trigeminal nucleus caudalis and thalamus.
• C. The resolution of the migraine attack.
• D. The aura phase.

Answer: B. Central sensitization within the trigeminal nucleus caudalis and thalamus.

12. The “gepants” (e.g., ubrogepant) represent a newer class of acute migraine medication. Their mechanism of action is:

• A. Serotonin 5-HT1B/1D agonism.
• B. CGRP receptor antagonism.
• C. Dopamine antagonism.
• D. Beta-adrenergic blockade.

Answer: B. CGRP receptor antagonism.

13. Cortical Spreading Depression (CSD) begins in which part of the brain, explaining the visual symptoms common in migraine aura?

• A. The brainstem
• B. The cerebellum
• C. The frontal lobe
• D. The occipital lobe

Answer: D. The occipital lobe

14. Which neurotransmitter system has a complex and multifaceted role in migraine pathophysiology, serving as the target for the triptan class of drugs?

• A. The dopaminergic system
• B. The serotonergic (5-HT) system
• C. The cholinergic system
• D. The histaminergic system

Answer: B. The serotonergic (5-HT) system

15. Migraine is fundamentally considered a disorder of the:

• A. Musculoskeletal system.
• B. Cardiovascular system.
• C. Central and peripheral nervous system.
• D. Endocrine system.

Answer: C. Central and peripheral nervous system.

16. Common migraine “triggers” like stress or lack of sleep are thought to initiate an attack by:

• A. Directly causing vasodilation.
• B. Increasing an individual’s susceptibility to trigeminovascular activation.
• C. Causing a permanent change in DNA.
• D. Immediately causing an aura in all patients.

Answer: B. Increasing an individual’s susceptibility to trigeminovascular activation.

17. The sensation of pain in a migraine attack is primarily transmitted by which cranial nerve?

• A. The optic nerve (CN II)
• B. The facial nerve (CN VII)
• C. The vagus nerve (CN X)
• D. The trigeminal nerve (CN V)

Answer: D. The trigeminal nerve (CN V)

18. The development of monoclonal antibodies that target CGRP or its receptor is based on the pathophysiological understanding that CGRP is:

• A. Only released after the headache has subsided.
• B. A key mediator of the pain and vasodilation in a migraine attack.
• C. An anti-inflammatory peptide.
• D. Responsible for the visual aura.

Answer: B. A key mediator of the pain and vasodilation in a migraine attack.

19. How does the pathophysiology of migraine differ from that of a tension-type headache?

• A. Tension-type headache involves significant neurogenic inflammation and aura.
• B. Migraine pathophysiology involves specific activation of the trigeminovascular system, while tension-type headache is thought to involve more peripheral and myofascial pain mechanisms.
• C. The two have identical pathophysiological mechanisms.
• D. CGRP is not involved in migraine.

Answer: B. Migraine pathophysiology involves specific activation of the trigeminovascular system, while tension-type headache is thought to involve more peripheral and myofascial pain mechanisms.

20. The brainstem is thought to be the “migraine generator” in some theories because it:

• A. Controls vision.
• B. Is the source of the CGRP release.
• C. Contains nuclei that regulate pain perception and cranial blood flow, which may be dysfunctional in migraine patients.
• D. Is where auras originate.

Answer: C. Contains nuclei that regulate pain perception and cranial blood flow, which may be dysfunctional in migraine patients.

21. A patient with frequent migraines may experience “central sensitization.” This means:

• A. Their pain threshold becomes higher over time.
• B. Their neurons become more responsive to painful and non-painful stimuli, leading to more severe and persistent pain.
• C. They become less sensitive to triggers.
• D. Their peripheral nerves are solely responsible for the pain.

Answer: B. Their neurons become more responsive to painful and non-painful stimuli, leading to more severe and persistent pain.

22. An understanding of migraine pathophysiology is essential for the pharmacist to:

• A. Explain to the patient why certain medications are used and how they work.
• B. Make a definitive diagnosis of migraine.
• C. Perform brain surgery.
• D. Prescribe controlled substances.

Answer: A. Explain to the patient why certain medications are used and how they work.

23. The role of dopamine in migraine pathophysiology is suggested by the presence of which symptoms in some patients?

• A. Visual aura
• B. A throbbing headache
• C. Nausea, vomiting, and yawning
• D. Cutaneous allodynia

Answer: C. Nausea, vomiting, and yawning

24. The transformation from episodic to chronic migraine is thought to involve what pathophysiological change?

• A. A decrease in central sensitization.
• B. A permanent state of trigeminal nerve activation and central sensitization.
• C. The resolution of all triggers.
• D. An increase in the brain’s pain threshold.

Answer: B. A permanent state of trigeminal nerve activation and central sensitization.

25. A patient with migraine with aura has a contraindication to using combined hormonal contraceptives. This is due to a small but significant increased risk of:

• A. Ischemic stroke
• B. Weight gain
• C. Depression
• D. Kidney stones

Answer: A. Ischemic stroke

26. The pathophysiology of medication-overuse headache involves:

• A. The medication becoming more effective over time.
• B. A paradoxical state where the acute medication, when used too frequently, starts to lower the headache threshold and perpetuate the headache cycle.
• C. An allergic reaction to the medication.
• D. The medication being completely cleared from the body too quickly.

Answer: B. A paradoxical state where the acute medication, when used too frequently, starts to lower the headache threshold and perpetuate the headache cycle.

27. The efficacy of some prophylactic migraine medications like beta-blockers and antiepileptics is thought to be due to their ability to:

• A. Directly block CGRP release.
• B. Raise the threshold for migraine activation by stabilizing neuronal membranes and modulating neurotransmitter systems.
• C. Act as potent vasoconstrictors.
• D. Only treat the pain once it starts.

Answer: B. Raise the threshold for migraine activation by stabilizing neuronal membranes and modulating neurotransmitter systems.

28. The medicinal chemistry of the triptans focused on creating molecules that were selective for which serotonin receptors to minimize side effects?

• A. 5-HT2A and 5-HT2C
• B. 5-HT3
• C. 5-HT1B and 5-HT1D
• D. 5-HT4

Answer: C. 5-HT1B and 5-HT1D

29. In the etiology of migraine, hormonal fluctuations are a key trigger, especially for menstrual migraine. This is linked to the drop in which hormone?

• A. Progesterone
• B. Testosterone
• C. Estrogen
• D. Prolactin

Answer: C. Estrogen

30. The “Assess” step of the PPCP for a migraine patient would involve:

• A. Recommending a triptan immediately.
• B. Evaluating the frequency, severity, and characteristics of the headaches to differentiate it from other headache types.
• C. Creating a long-term plan.
• D. Dispensing the medication.

Answer: B. Evaluating the frequency, severity, and characteristics of the headaches to differentiate it from other headache types.

31. The release of CGRP from trigeminal nerve endings causes vasodilation by acting on CGRP receptors located on:

• A. Neuronal cell bodies.
• B. Smooth muscle cells of cranial blood vessels.
• C. The myelin sheath.
• D. Astrocytes in the brain cortex.

Answer: B. Smooth muscle cells of cranial blood vessels.

32. Cortical Spreading Depression (CSD) is a wave of depolarization followed by a period of:

• A. Intense neuronal firing.
• B. Prolonged suppression of neuronal activity.
• C. Increased blood flow.
• D. Normal brain activity.

Answer: B. Prolonged suppression of neuronal activity.

33. The pain of migraine is referred to the head and face because the trigeminal nerve provides sensory innervation to these areas.

• A. True
• B. False

Answer: A. True

34. The development of prophylactic monoclonal antibodies against CGRP was a direct result of understanding its central role in:

• A. The etiology of aura.
• B. The pathophysiology of migraine pain.
• C. The cause of medication-overuse headache.
• D. The metabolism of triptans.

Answer: B. The pathophysiology of migraine pain.

35. A key difference between the pathophysiology of acute and chronic migraine is the degree of:

• A. CGRP involvement.
• B. Trigeminal nerve activation.
• C. Central sensitization.
• D. Vasodilation.

Answer: C. Central sensitization.

36. The “unstable” brain of a migraineur refers to the concept that their brain has a ___________ to trigeminovascular activation compared to a non-migraineur.

• A. higher threshold
• B. lower threshold
• C. complete lack of a threshold
• D. threshold that never changes

Answer: B. lower threshold

37. Which of the following is NOT considered a primary phase of a migraine attack?

• A. Premonitory/Prodrome
• B. Aura
• C. Postdrome
• D. Interictal phase (the time between attacks)

Answer: D. Interictal phase (the time between attacks)

38. Why are triptans contraindicated in patients with a history of ischemic stroke or coronary artery disease?

• A. Because their mechanism of action includes vasoconstriction, which could be dangerous in these patients.
• B. Because they are not effective in these patients.
• C. Because they cause severe sedation.
• D. Because they interact with all cardiovascular medications.

Answer: A. Because their mechanism ofaction includes vasoconstriction, which could be dangerous in these patients.

39. The pathophysiology of migraine involves a complex interplay between the central nervous system and the:

• A. Gastrointestinal system.
• B. Peripheral vascular system.
• C. Cranial vasculature.
• D. Renal system.

Answer: C. Cranial vasculature.

40. A patient reports feeling fatigued and having difficulty concentrating for a day after their migraine headache resolves. This is known as the:

• A. Aura phase.
• B. Prodrome phase.
• C. Postdrome phase.
• D. Ictal phase.

Answer: C. Postdrome phase.

41. The rationale for using NSAIDs in the acute treatment of mild-to-moderate migraine is to:

• A. Block CGRP release.
• B. Inhibit the inflammatory cascade by blocking prostaglandin synthesis.
• C. Cause vasoconstriction.
• D. Prevent central sensitization.

Answer: B. Inhibit the inflammatory cascade by blocking prostaglandin synthesis.

42. Which brain structure acts as a key relay station for sensory information, including pain signals from the trigeminal nerve?

• A. The cerebellum
• B. The hippocampus
• C. The thalamus
• D. The amygdala

Answer: C. The thalamus

43. The “trigeminal nucleus caudalis” located in the brainstem is a critical site for:

• A. The initiation of aura.
• B. The processing of migraine pain signals before they are relayed to the thalamus.
• C. The release of CGRP.
• D. The vasoconstrictive effects of triptans.

Answer: B. The processing of migraine pain signals before they are relayed to the thalamus.

44. The understanding that migraine is a neurological disorder helps explain why:

• A. It is often accompanied by symptoms like photophobia, phonophobia, and nausea.
• B. It can be treated with over-the-counter pain relievers alone in all cases.
• C. It is not considered a disabling condition.
• D. The pain is not real.

Answer: A. It is often accompanied by symptoms like photophobia, phonophobia, and nausea.

45. The fact that prophylactic medications for migraine come from diverse drug classes (e.g., antihypertensives, antidepressants, anti-seizure medications) suggests that:

• A. The pathophysiology is simple and involves only one pathway.
• B. The pathophysiology is complex and can be modulated at multiple points.
• C. These drugs all have the same mechanism of action.
• D. The choice of prophylactic agent does not matter.

Answer: B. The pathophysiology is complex and can be modulated at multiple points.

46. A “trigger” is a factor that can increase the likelihood of a migraine attack in a susceptible individual. It is not the underlying:

• A. Symptom
• B. Cause
• C. Treatment
• D. Aura

Answer: B. Cause

47. The “medicinal chemistry of drugs used in migraine” is a lecture in the curriculum because:

• A. It helps students learn how to synthesize triptans.
• B. It explains how the molecular structure of these drugs allows them to interact with specific targets like 5-HT1B/1D or CGRP receptors.
• C. It is a topic for researchers only.
• D. It is required for legal reasons.

Answer: B. It explains how the molecular structure of these drugs allows them to interact with specific targets like 5-HT1B/1D or CGRP receptors.

48. Which of the following is NOT a proposed mechanism for the prophylactic effect of topiramate in migraine?

• A. Enhancement of GABA-mediated inhibition.
• B. Antagonism of glutamate receptors.
• C. Potent agonism at serotonin 5-HT1B/1D receptors.
• D. Blockade of voltage-gated sodium channels.

Answer: C. Potent agonism at serotonin 5-HT1B/1D receptors.

49. The pathophysiology of migraine is an active area of research, leading to the development of:

• A. No new therapies in the last 30 years.
• B. Novel targeted therapies like CGRP antagonists.
• C. Only stronger opioid medications.
• D. Only more potent triptans.

Answer: B. Novel targeted therapies like CGRP antagonists.

50. An understanding of the etiology and pathophysiology of migraine allows the pharmacist to:

• A. Make a definitive medical diagnosis.
• B. Better counsel patients on their condition and the rationale for their treatment plan.
• C. Prescribe prophylactic medications.
• D. Perform neurological examinations.

Answer: B. Better counsel patients on their condition and the rationale for their treatment plan.