A 14-year-old, previously healthy girl is brought to the office due to recurrent headaches. The patient has had 4 episodes of severe, throbbing pain on the right side of her head over the last 2 months, with the most recent occurring a week ago. The headaches are often associated with nausea, and the patient has had occasional vomiting. Lying in a dark room and taking acetaminophen improve the pain. The episodes resolve after 4-5 hours. The patient has had no visual disturbances or focal weakness but has tingling and numbness on the right upper extremity prior to the headaches. Vital signs are within normal limits. Physical examination, including funduscopic and neurologic examination, shows no abnormalities. Which of the following is most likely involved in the pathogenesis of this patient's current condition?

Question

A 14-year-old, previously healthy girl is brought to the office due to recurrent headaches.  The patient has had 4 episodes of severe, throbbing pain on the right side of her head over the last 2 months, with the most recent occurring a week ago.  The headaches are often associated with nausea, and the patient has had occasional vomiting.  Lying in a dark room and taking acetaminophen improve the pain.  The episodes resolve after 4-5 hours.  The patient has had no visual disturbances or focal weakness but has tingling and numbness on the right upper extremity prior to the headaches.  Vital signs are within normal limits.  Physical examination, including funduscopic and neurologic examination, shows no abnormalities.  Which of the following is most likely involved in the pathogenesis of this patient's current condition?

Quizplus · Accepted Answer

11ec160b_3b09_9e35_9249_c5793dd42319_MD0001_00 This patient with a normal neurologic examination has episodic, throbbing, unilateral headaches associated with nausea, vomiting, and light sensitivity; findings characteristic of migraines. An aura may precede the headache in some patients and is most commonly visual (eg, scotoma) or sensory (eg, unilateral extremity paresthesia). The pathogenesis of migraines is multifactorial with a genetic predisposition to increased cerebral excitability, allowing a wave of cortical spreading depression to propagate across the cerebral cortex. Cortical spreading depression is likely involved in generating the pre-migraine aura and is associated with the abnormal activation of trigeminal afferents, which extend to the meninges and intracranial vasculature. This activation results in the release of calcitonin gene-related peptide (CGRP), a neuropeptide involved in pain transmission. CGRP also causes local vasodilation and increased neurogenic inflammation, which can further sensitize trigeminal afferents and increase pain. The role of CGRP in migraine pathogenesis has been supported by the effectiveness of triptans ([5-HT_1B/1D] receptor agonists that decrease CGRP release) and anti-CGRP antibodies (eg, erenumab) in treating migraine headaches. (Choice A) Pheochromocytoma is a catecholamine-producing adrenal medullary tumor that causes brief (<1 hr) episodic headaches associated with sweating, palpitations, and hypertension (rather than an aura). (Choice B) Amplification of epidermal growth factor receptors is associated with the development of astrocytoma and glioblastoma. Headache and vomiting due to increased intracranial pressure are common but typically associated with other neurologic manifestations (eg, seizures, focal neurologic deficits). (Choice C) Orexin A and B are excitatory neuropeptides that are produced in the lateral hypothalamus during wakefulness and inhibit the transition to REM sleep. Instead of episodic headaches, deficiency of these neuropeptides causes the daytime sleepiness, inappropriate bouts of REM sleep (ie, sleep attacks), and emotionally triggered transient muscle weakness (ie, cataplexy) seen in narcolepsy. (Choice D) Dysfunction of the thalamocortical fiber calcium channels can contribute to the development of absence seizures, which are brief (10-20 sec) staring episodes with impairment of consciousness, not recurrent headaches. Educational objective: Migraines are episodic, unilateral, throbbing headaches associated with nausea, vomiting, and sensitivity to light. The pathogenesis of migraines involves a genetic predisposition to increased cerebral excitability (eg, cortical spreading depression), which leads to abnormal neuronal activation of trigeminal afferents and the release of calcitonin gene-related peptide, a vasoactive neuropeptide involved in the transmission of pain signals. __________ References: The trigeminovascular pathway: role of CGRP and CGRP receptors in migraine. (http://www.ncbi.nlm.nih.gov/pubmed/28485848) An update on migraine: current understanding and future directions. (http://www.ncbi.nlm.nih.gov/pubmed/28321564)

A 14-Year-Old, Previously Healthy Girl Is Brought to the Office