Headaches

Question 1

Tension-type Headache Epidemiology

Answer 1

30-80% prevalence
Episodic < 180/year
Chronic > 180/year
Onset < age 40
More common in women
Increased prevalence with increased educational attainment

Question 2

Tension Headache Pathophysiology

Answer 2

Muscle contraction
Greater occipital nerve compression
Exacerbated by emotional stress

Question 3

Tension Headache Clinical Presentation

Answer 3

30 min – 1 week
Pressing/tightening 
Mild to moderate intensity
Bilateral
Not aggravated by routine physical activity
No nausea or vomiting!
Phono or photophobia, but not both

Question 4

Tension Headache Management

Answer 4

Often self-treated
Analgesics (ibu, asa, apap)
Acupuncture
Biofeeback
Relaxation technique
Other modalities

Question 5

Cluster Headache Epidemiology

Answer 5

Male:female 4:1
Mean onset age 27-31
Incidence 2.5/100,000/year
Prevalence ~ 1/1000

Question 6

Cluster Headache Pathophysiology

Answer 6

Incompletely understood
Hypothalamic activation of trigeminovascular autonomic system
Genetics
Positive FH in 7-11%
R>L shunt/PFO?
short duration: 15 min to 2 hrs

Question 7

Cluster Headache Clinical Presentation

Answer 7

Severe, unilateral, orbital, supraorbital or temporal pain lasting 15-180 minutes
Circadian periodicity
Frequency: every other day to 8/day
Autonomic symptoms:
Lacrimation, nasal congestion, rhinorrhea, forehead sweating, miosis, ptosis, eyelid edema, conjunctival injection

Question 8

Cluster Headache Management

Answer 8

Oxygen 6-10 L/min for 15 min
Sumatriptan subQ/nasal
Zolmitriptan nasal
Prophylaxis of episodic clusters
Verapamil, melatonin, prednisone, capsaicin
oral takes too long to be absorbed

Question 9

Migraine Headache Epidemiology

Answer 9

Female:male 3:1
Onset age < 40
Prevalence 18% women, 6% men
Lifetime prevalence 20 – 25%
>50% people with migraines miss > 2 days of work/month

Question 10

Migraine Headache Pathophysiology

Answer 10

Uncertain
Possible spreading cortical depression
Possible neurotransmitter dysfunction
NO or CGRP
Possible dorsal pontine activation

Question 11

Migraine Headache Clinical Presentation

Answer 11

Typical symptoms – intermittent, unilateral, throbbing, crescendo-decrescendo headache lasting hours to days, gradual onset, associated with nausea; + family history helpful
Aura +/-

Question 12

Migraine Headache Genetics

Answer 12

Positive family history common
Familial hemiplegic migraine
1/5 have associated nystagmus or ataxia
CACNA1A gene (neuronal ca++ channel)

Question 13

Migraine Headache medication hx

Answer 13

Avoid OCPs in migraine with aura
Avoid Sildenafil?
There is an increased risk of stroke in patients who have migraine with aura, this risk is increased with the use of estrogen containing oral contraceptives. In my practice, if a woman has migraine with aura, I will not prescribe estrogen-containing birth control methods and instead recommend IUDs or barrier methods.Obstet

Question 14

Migraine Headache1st line Treatment for Attacks

Answer 14

Triptans
DHE
Perchlorperazine, metoclopramide
Apap, ibu, naproxen
Dexamethasone

Question 15

Migraine Prevention

Answer 15

Prevent MOH
Refractory HA
Predictable HA
Hemiplegic or Basilar Migraine

While triptans and DHE are effective for relieving an acute attack, they are less helpful in preventing attacks. Frequent use of over-the-counter analgesics, triptans, and opioids significantly increases the risk for medication overuse headache. MOH is challenging to treat and can be debilitating for patients. In general, if a patient is treating acute migraine more than twice/month it is appropriate to consider use of preventive medications. Prevention is also appropriate for people who have headaches that are not responsive to abortive therapy and for people who have predictable headaches, as in women who get menstrual migraines. Preventive strategies are also appropriate for people who have hemiplegic or basilar migraine, for which triptans are not indicated.

Question 16

Serotonin

Answer 16

Serotonin or 5-hydroxytryptaine is a centrally acting neurotransmitter with a number of significant peripheral actions as well. It regulates smooth muscle in the GI tract and cardiovascular systems and plays a role in platelet aggregation. There are at least 14 serotonin receptor subtypes that can serve as targets for medications and drugs.

Question 17

5-HT Synthesis & Metabolism

Answer 17

Serotonin is synthesized from the essential amino acid tryptophan and stored in secretory granules in serotonergic neurons. Activation of those neurons releases serotonin through exocytosis. In the nervous system, the activation of released serotonin is terminated by reuptake into the axon terminal via a specific transporter. This same transporter is responsible for uptake of serotonin into platelets. Serotonin is primarily metabolized by monoamine oxidase and aldehyde dehydrogenase into 5- hydroxyindole acetic acid (5-HIAA). 5HIAA is actively transported out of the brain, by a process that is inhibited by probenecid. The role of MAO in metabolism of 5HT is the reason for the drug interactions between SSRIs and MAO inhibitors.

Question 18

5-HT in CNS

Answer 18

Sleep-wake cycle regulation, aggression & impulsivity, cognition, sensory perception, motor activity, temperature regulation, nociception, mood, appetite, sexual behavior & hormone secretion.

Question 19

5-HT in GI Tract

Answer 19

Produced & stored in enterochromaffin cells of gastric mucosa
Released in response to mechanical stretch, eg eating, and vagal stimulation
Metabolized by MOA in liver
Uptake by platelets

Question 20

5-HT in CV System

Answer 20

Constriction of cerebral vasculature

Constriction of splanchnic, renal & pulmonary vasculature

Question 21

Role of Serotonin in Migraine

Answer 21

[5-HT] vary in migraine attack
Increased 5-HT levels as trigger
5-HT1 agonists as treatment

While the complete pathophysiology of migraine headache is unknown, there is evidence that serotonin plays a key role. (Mehrotra et al, 2008). Plasma and platelet concentrations of serotonin vary with the different phases of a migraine attack and urinary concentrations of serotonin and its metabolites are elevated during migraine attacks. Medications that release serotonin can precipitate migraine attacks and serotonin receptor agonists are effective in management of acute migraine.

Question 22

Triptans

Answer 22

Triptans are selective agonists of the 5-HT1b and 5-HT1d receptors and are effective for acute migraine treatment. Triptans help abort the attack, alleviate pain and decrease nausea and vomiting that is common in migraines. Because of our incomplete understanding of the exact cause of migraines, we are not sure exactly how triptans work to relieve symptoms. Triptan-mediated activation of the 1b and 1d serotonin receptors causes vasoconstriction of the cerebral vasculature and activation of the 1b and 1d receptors modulates neurotrasmitter release which may block release of proinflammatory neuropeptides.

Question 23

Triptans Pharmacokinetics

Answer 23

Triptans are metabolized by MOA in the liver and excreted both as unchanged drug and active and inactive metabolites in the urine and feces. Most triptans have a relatively short half-life of about 1-3 hours, although the half-life of naratriptan approaches 6 hours and the half-life of frovatriptan is 26 hours. Frovatriptan seems to be less effective than other triptans for acute migraine attack to to longer time to peak plasma concentrations.

Question 24

Triptan Contraindications

Answer 24

Triptans generally constrict vessels and can cause vasospasm. Because of this, they are contraindicated in patients with CAD, including Printzmetal’s angina, hemiplegic or basilar migraines, stroke and ischemic bowel disease.
Triptans can also cause increased blood pressure and are contraindicated in patients with uncontrolled blood pressure.
Triptans should not be used in people who have taken MAO-inhibitors in the past 2 weeks or in patients who have or will take ergots or other triptans within 24 hours. Because of hepatic metabolism, triptans are also contraindicated in people with hepatic impairment.

Question 25

Ergots

Answer 25

Fungal product
DHE
Nausea & vomiting
Avoid in vascular, hepatic, renal disease
CYP3A4 interactions

Question 26

Sudden onset, severe “Thunderclap” headache

Answer 26

Subarachnoid hemorrhage

Question 27

Headache onset with exercise

Answer 27

Ruptured aneurysm

Question 28

New HA onset after age 50

Answer 28

Temporal arteritis, intracranial mass

Question 29

HA with fever, stiff neck, photophobia, systemic signs

Answer 29

Meningitis, encephalitis

Question 30

HA onset hours to weeks after trauma

Answer 30

Subdural hematoma

Question 31

HA with focal neurologic signs, symptoms or papilledema

Answer 31

Tumor, subdural hematoma, epidural bleed

Question 32

Multiple people with similar new onset HA, eg family, coworkers

Answer 32

Environmental exposure, carbon monoxide