Download Headaches on the RITE: or, the RITE is a headache

What a Long, Strange
Triptan It’s Been
Ryan Jacobson
Headaches for the RITE
Worst headache of life, artist’s
depiction
This Lecture: Why & What
• Identified as an area of deficiency in many years
• Many questions pertain to headache pathophysiology and management
each year
• Case-based scenarios and review based on data from the last 4ish years
Case 1
• A 29-year-old baker has been busy tasting
pies. Eventually he develops symptoms of
flushing, palpitations, tingling in his
extremities, and a severe headache. He is
hallucinating. He does not have a history of
migraine. Which ingredient has he overindulged in?
Case 1
• Nutmeg.
• Mediated by a chemical in nutmeg myristicin,
which acts as a hallucinogen
• Symptoms improve over several hours.
Benzodiazepines can be used for agitation
• Tested multiple times
Case 2
• A 29-year-old woman with no previous history
presents with a left-sided headache. Photophobia
and vomiting are present. She endorses seeing
flashing lights in her vision, a symptom that
began just before the headache. She notes poor
sleep over the previous 3 days. Family history
notable for sister with migraine.
• Exam: afebrile. no papilledema. No nuchal
rigidity.
• What is your next step?
–
–
–
–
Lumbar puncture
PET scan
IV phenytoin load
Triptan
Case 2
•
Migraine
•
Can treat for migraine with triptan. Triptans work at 5HT1 receptors, 1b 1d
subtypes.
•
Remember triptans are contraindicated with known CAD
•
Note: if they give you a scenario where a woman is being abused and has
migraines, address the abuse first. Tested 2013.
•
“This patient's symptoms are most compatible with migraine. There are no
features of her history or examination to suggest a more serious underlying
disorder such as meningitis, subarachnoid hemorrhage, or a space occupying
lesion. Parenteral symptomatic therapy is warranted of which sumatriptan would
likely be most effective.”
Case 3
• A 43 year old man presents with head pain
that wakes him up in the early morning hours.
He describes pain behind his right eye that
occurs in severe attacks. He has noticed tears
coming out of the right eye during the attacks.
• He cannot provoke episodes by touching the
right side of his face. He denies trauma.
Case 3
• Cluster Headache
• There is an association with smoking.
• Oxygen should abort headache. DHE less
effective. Prednisone can potentially prevent
recurrence of headache.
• “What can prevent the next headache?”
• We will re-visit some details of cluster
headache in a few slides
Case 4
• A 33-year-old woman presents for evaluation
of episodes of head pain. She has not seen a
doctor for these, because the attacks of pain
only last about 5-8 minutes. The pain is
located over her left eye and temple. During
the attacks, she has noticed some discharge
from her left eye and nose on some occasions.
Which treatment should be offered?
Case 4
•
•
•
•
•
•
•
The diagnosis is paroxysmal hemicrania.
Some autonomic features.
The headaches are Indomethacin responsive.
“Side-locked”
Minutes long, several times a day.
More common in women.
Tested multiple times, essentially every year
Contrast with Hemicrania
Continua
• Constant unilateral headache, temporal or
periorbital
• Also more common in women
• Can have exacerbations that sound migrainous
or cluster-like
• Child with hemicrania continua was on 2011
exam. Adult in 2012. Child in 2015 (why?!)
• Also indomethacin responsive (by definition)
•
“A continuous, unilateral headache is most likely hemicrania continua, one
of the trigeminal cephalgias. It is very responsive to indomethacin, and this
can be used as both a treatment and diagnostic trial.”
Contrast with Cluster Headache
• More common in men
• Associated with smoking (appears to have
been tested in 2012)
• Remember, oxygen is useful. This was
tested in 2012 and 2013.
• Time duration between that of paroxysmal
hemicrania and hemicrania continua
Case 4-A
• A 33-year-old man presents with unusual head pains. He
says that he gets sudden bouts of brief of right eye and
temple pain. They are so short, that they last for one
commercial on TV.
Nothing provokes them. His wife notes that he has no pain
tolerance, since tears are always coming out of his right
eye during the episodes of pain. What is the best
diagnosis, and what are the next steps?
Case 4A
• SUNCT – short-lasting unilateral neuralgiform
headache with conjunctival injection and hearing
• Think BUNCT - these are the briefest of the
TACs - 5-240 seconds
• Conjunctival injection and tearing prominent in
story
• SUNCT (5-240 seconds) < Paroxysmal
Hemicrania (women!) < Cluster < Hemicrania
Continua
Case 4A, continued
• In SUNCT, consider imaging to rule out skull
base lesion.
• Some role for IV Lidocaine
Does patient have HA?
Not Just a Headache?
Just a Headache?
MELAS INFECTION CADASIL SAH
MIGRAINOUS
POSITIONAL/MENINGEAL ENHANCEMENT
CSF HYPOTENSION. RECOMMEND
PAPILLEDEMA/OBESE
AUTONOMIC/TAC
PSEUDOTUMOR.
Consider if on Vitamin
BLOOD PATCH.
A derivatives.
DID I MISS SOMETHING… IS IT A TAC?
NO
YES
MAN/MANY MINUTES
PROPHYLACTIC NEEDED? ABORTIVE NEEDED?
-TRIPTAN IF NO C/I
WOMAN/SECONDS-MINUTES
SUNCT
PAROXYSMAL HEMICRANIA HEMICRANIA CONTINUA
-DISCONTINUE OFFENDING
AGENT
-NO VPA IF WOMAN.
OXYGEN
-AVOID BB IN ASTHMA
WOMAN/CONTINUOUS
MEDICATION OVERUSE?
CLUSTER
-CONSIDER TOPIRAMATE.
MAN/FEW SECONDS
INDOMETHACIN
Consider lidocaine
Case 5
• A 76-year-old retired horticulturist presents for
evaluation of headaches. She is distraught, as she
has never had headaches before. She has pain
over the right temple. The pain has been
worsening over time. She has lost weight in the
past 10 days, because her jaw and tongue hurt
with chewing.
• Review of Systems notable for fatigue and
shoulder aches
• What are your next steps, and in which order?
Case 5
• The diagnosis is temporal arteritis.
• Next steps:
– Check ESR
– Give steroids urgently
– Temporal artery biopsy to follow as soon as
possible
2014: steroids before biopsy may result in scar
tissue rather than inflammation in biopsy
specimen
Case 6
•
A 38-year-old migraineur has been relatively headache free for the last 6 months.
She slips on an icy sidewalk, striking her neck. She now has a new type of
headache, described as severe, diffuse head pain. Associated features include
nausea and tinnitus. She notes that the pain is 10/10 when upright, and 1/10
when supine. Her MRI is shown.
Case 6
• Answer: intracranial hypotension.
• They have given a traumatic precipitant.
• Imaging shows diffuse dural enhancement.
(HOPEFULLY they give you an image with
smooth, diffuse enhancement to steer you
away from cancer)
• If no image is given, they want you to identify
it with MR imaging or CT myelogram. Do not
go for LP or cytology.
Case 6 continued
• The patient wishes for a medication that
will be safe with breast feeding. Which of
the following is the safest option?
• 1. Aspirin
• 2. Heavy duty barbituates
• 3. Sumatriptan
• 4. Amitriptyline
• 5. Hydrocodone-Acetaminophen
Case 6 continued
• They want you to say that narcotics are
safest.
• While the amount of most drugs excreted in breast
milk is 1% to 2% of the maternal dose, there is some
variability depending on both the drug's
characteristics and breast milk's characteristics.
Barbiturates may cause sedation; aspirin is
considered less safe than acetaminophen; triptans
and tricyclic antidepressants are of unknown risk to
the infant; while narcotics are safe.
Case 7
• In peds clinic you see 2 patients -
• Patient 1 Savannah is a 9 year old girl with frequent headaches for
the past 2 months. They are located over the temple, and occasional
cause vomiting. They are getting no better. Exam is normal.
• Patient 2 Dylan is a 10 year old boy with headaches for the past 2
months. They are gradually worsening. When the headache is most
severe, he loses vision. Examination is notable for right hemibody
ataxia.
• Which one needs imaging?
Case 7
• The second patient (obviously)
• “The majority of children with recurrent
headaches, with complete clearing between
episodes, do not need neuroimaging. The
following would mandate neuroimaging in a child
presenting with headaches: auras lasting more
than an hour, persistent neurologic findings,
abnormal neurologic exam between headaches,
predominantly occipital headaches, loss of
vision at headache peak, or recent significant
change in headache pattern.”
Case 7 continued
• Which treatment is best for Patient 1?
• Dietary Modification? Sumatriptan?
Valproate? Stress Management?
Topiramate?
Case 7 continued
• Which treatment is best for Patient 1?
• Dietary Modification? Sumatriptan?
Valproate? Stress Management? Topiramate?
• Prescribe topiramate instead of valproate in a
young woman for a prophylactic medication.
Choose a medication over a behavioral
modification.
Case 7 continued
• Savannah comes back 6 months later.
She notes episodic flank pain and
hematuria. Which of the following is most
likely responsible?
• -struvite stones
• -calcium phosphate stones
• -calcium oxalate stones
• -stress reaction
Case 7 continued
• Calcium oxalate stones.
• Remember - “topamaxalate”
• Tested multiple times
Other Topiramate side effects?
Paresthesias, Cognitive Symptoms, Fatigue,
Insomnia, Loss of appetite, anxiety, dizziness
• Savannah’s mom also requests a triptan in
addition to the topiramate. Which one has the
longest half life?
Case 7 Continued
• Savannah’s mom also requests a triptan in
addition to the topiramate. Which one has
the longest half life?
-Frovatriptan has the longest half life “Frova”
- 26 hours
Was on the test twice in 2015. Why, I don’t
know. I’m just giving the lecture.
Triptans
• Fast Onset, High Efficacy at 2 hours
– Sumatriptan, zolmitriptan, rizatriptan,
almotriptan, eletriptan
• Slow onset, lower response rate at 2 hours
– Naratriptan (Amerge), frovatriptan
Case 7, continued.
• Savannah the migraineur’s history is most
likely to include the following?
• -Episodes of extremities turning red
• -Episodes of dizziness/vertigo
• -Episodes of teeth itching
• -Gravel in the stool
• -Transient Monocular Vision loss
• -Giraffe bite between ages of 18 months
and 3 years
Case 7, continued.
• -Episodes of Dizziness/Vertigo
• “benign paroxysmal vertigo, a syndrome that
occurs in children in the first 5 years of life and
is a frequent precursor of migraine.
Investigations (MRI, EEG) are normal. The
episodes usually resolve by the end of the first
decade.”
Case 8
• A 34-year-old woman has never had headaches
before. Over the past 3 months, she has had a
constant headache located over both temples,
6/10 in severity. There is no photophobia or
nausea. Of note, she had a febrile illness with
lymphadenopathy in the two weeks before this
illness started.
• What is the best diagnosis?
Case 8
• New daily persistent headache.
• Do not have a history of headaches and
gradual worsening
• May be related to viral infection around the
time of headache onset.
Case 9
• A 43-year-old man presents with
headaches and abnormal brain MRI. He
has headaches 3 times per week,
unilateral, throbbing, and associated with
photophobia and phonophobia. His MRI is
shown.
Case 9
•
•
•
•
What should you advise?
1. Admit now, consult neurosurgery
2. Refer to neurosurgery as an outpatient.
3. Reassure.
Case 9
•
Reassure. It’s a Developmental Venous Anomaly. It is incidental.
•
A developmental venous anomaly (DVA) or venous angioma is occasionally identified
in the work-up of patients with neurological symptoms. Headache is the most
common symptom. Seizures are also commonly associated. There is no real
evidence, however, that either headaches or seizures are caused by the DVA, and in
most instances the DVA is incidental. It is very important to understand that the DVA
represents the venous drainage of the brain tissue in which it is situated. Removal of
the DVA may cause a venous infarction.
•
Radiographically these can have a “caput medusae” type appearance, are common
around the periventricular white matter, and will be more obvious on post-contrast
images.
Case 10
• A migraine patient comes to clinic. His
medication list includes:
• -Sumatriptan
• -Fentanyl Patch
• -Butalbital
• -Lisinopril
• -Lamotrigine
• He complains of increased sweating. Also he
has rebound headaches. Which medications are
most likely responsible?
Case 10, continued.
• Fentanyl and opioid agonists can be associated
with hyperhidrosis
• Lamotrigine, lisinopril, triptan “should not cause
rebound headache”
• Medication overuse headache tested in
2011/2012 - “often responds to withdrawal of minor analgesics, with or
without the addition of prophylactic medication.”
Case 11
• A 23-year-old woman presents to clinic
and has been getting 4 headaches per
week. PMHx is notable for asthma and
Raynaud’s phenomenon. Which
medication is best?
• Propranolol
• Verapamil
• Depakote
• Prednisone
• Homeopathic Remedies
Case 11
• Choose Verapamil - remember that beta
blockers are contraindicated in asthma,
and not ideal in Raynaud’s.
• Read the question to see if they want you
to choose a prophylactic or abortive
• Do not choose VPA in a woman of child
bearing age
Case 12
• A 7-year-old girl presents with headaches and double
vision. She gets headaches twice weekly. They last for 2
hours. They are located over the right side of the head,
and can be accompanied by nausea and phonophobia.
She has a headache now. Exam is notable for aniscoria
with right pupil being larger, and slightly limited adduction
supraduction and infraduction of the right eye. What is
the best Diagosis?
• Aneurysm
• Complicated Migraine
• Myasthenia Gravis
• Miller-Fisher Syndrome
• Likely history of giraffe bite between 18 months and 3
years
Case 12
• Complicated Migraine
• “A partial third nerve palsy associated with headache in
young children is most commonly due to
ophthalmoplegic migraine. Cerebral aneurysms
presenting as a partial third nerve palsy would be
extremely unusual in young children. Myasthenia gravis
does not present with pain, and pupillary involvement
would be unusual. Cerebral aneurysm, Miller-Fisher
syndrome, and a brainstem tumor would have other
findings on careful neurologic examination.”
Case 13
A 23-year-old obese woman presents with
headaches and vision loss. Her fundoscopic
image is shown. Which medication does she
most likely take?
-Isotretinoin
-Amlodipine
-St. Johns Wort
-Ceftriaxone
Case 13
• Isotretinoin. Pseudotumor cerebri can be
associated with derivatives of Vitamin A.
• Tested 2012, 2013
Case 14
• A 33 year old woman presents with worst
headache of her life. She has a history of severe
migraines, but the headaches in the last week
have been worse. She has had at least 5
headaches in the past week, all of which began
like a sudden thunderclap. She had left hand
numbness which resolved, and her husband
noticed a right face droop which resolved. She
recently started a new medication.
• LP and CT head are normal. What is the most
likely diagnosis?
Case 14
• Diffuse Cerebral Vasoconstriction Syndrome
• (AKA RCVS, AKA Call Fleming). The RITE
appears to call it Diffuse Cerebral
Vasoconstriction Syndrome.
• Can result in SAH
• Story will sound like SAH - they want to know if
you’ll chase it or think of the diagnosis
• Angiogram will show segmental arterial
narrowing which improves over time.
• Tested 2X in 2014 and in 2015.
• Which medications are most commonly
responsible for attacks?
Case 14, continued
• SSRIs
• Any vasoactive medication can provoke
worsening symptoms
Case 15
•
A 33-year-old migraine patient calls at 5:05 pm for a refill of her
Tramadol. What is the mechanism of this drug?
1.
Works peripherally to decrease epinephrine release
2.
Works centrally at mu opioid receptors, inhibits norepinephrine
and serotonin reuptake.
3.
Works centrally at delta and kappa opioid receptors, inhibits
norephinephrine and serotonin reuptake.
4.
Decreases production of bad humors, particularly black bile
Case 15
• The correct answer is B
• Tested in 2014
• Tramadol, a centrally acting analgesic structurally related to
codeine and morphine, consists of two enantiomers, both of
which contribute to analgesic activity via different
mechanisms. (+)-Tramadol and the metabolite (+)-Odesmethyl-tramadol (M1) are agonists of the mu opioid
receptor. (+)-Tramadol inhibits serotonin reuptake and (-)tramadol inhibits norepinephrine reuptake, enhancing
inhibitory effects on pain transmission in the spinal cord. The
complementary and synergistic actions of the two
enantiomers improve the analgesic efficacy and tolerability
profile of the racemate.
Headache Greatest Hits
•
•
•
•
•
•
•
•
Cluster Headache - Give ‘em oxygen. Men.
SUNCT – The S is for Short. Men. Rule out skull base lesion.
Paroxysmal Hemicrania - women. Minutes long. Look for it.
Hemicrania Continua - continuous. Women. Indomethacin. MOST TACs on
exam MOST YEARS.
Pseudotumor - Vitamin A derivatives. May show fundoscopic picture.
Low Pressure headache - after an LP or fall. Diffuse dural enhancement.
Don’t say meningitis.
Medication Overuse headache - acetaminophen, caffeine, barbituates.
Solution, don’t use those things.
CADASIL - yes, migraine, but also focal symptoms, very abnormal imaging.
NOTCH3 mutation on chr.19.
Does patient have HA?
Not Just a Headache?
Just a Headache?
MELAS INFECTION CADASIL SAH
MIGRAINOUS
POSITIONAL/MENINGEAL ENHANCEMENT
CSF HYPOTENSION. RECOMMEND
PAPILLEDEMA/OBESE
AUTONOMIC/TAC
PSEUDOTUMOR.
Consider if on Vitamin
BLOOD PATCH.
A derivatives.
DID I MISS SOMETHING… IS IT A TAC?
NO
YES
MAN/MANY MINUTES
PROPHYLACTIC NEEDED? ABORTIVE NEEDED?
-TRIPTAN IF NO C/I
WOMAN/SECONDS-MINUTES
SUNCT
PAROXYSMAL HEMICRANIA HEMICRANIA CONTINUA
-DISCONTINUE OFFENDING
AGENT
-NO VPA IF WOMAN.
OXYGEN
-AVOID BB IN ASTHMA
WOMAN/CONTINUOUS
MEDICATION OVERUSE?
CLUSTER
-CONSIDER TOPIRAMATE.
MAN/FEW SECONDS
INDOMETHACIN
Consider lidocaine
Medication Overuse Headache
According to the International Classification of Headache Disorders,
2nd edition, the definition of medication overuse headache (MOH)
continues to evolve over time. The recently published new appendix
criteria for a broader concept of chronic migraine of the International
Headache Society define MOH as 1) headache present > 15
days/month; 2) regular overuse for 3 months of one or more
acute/symptomatic treatment drugs, defined as: ergotamine,
triptans, opioids, or combination analgesic medication on 10 days
/month on a regular basis for >3 months; or simple analgesics or
any combination of ergotamine, triptans, analgesics, opioids on 15
days/month on a regular basis for >3 months without overuse of any
single class alone.
-May use phenobarbital to help wean off barbituates.
CGRP
• Calcitonin gene-related peptide (CGRP) is derived, with calcitonin,
from the CT/CGRP gene located on chromosome 11. It is primarily
produced in nervous tissue; however, its receptors are expressed
throughout the body. It is found in every location described in
migraine genesis and processing, including meninges, trigeminal
ganglion, trigeminocervical complex, brainstem nuclei, and cortex. It
is released in animal models following stimulation of the CNS similar
to that seen in migraine, and triptans inhibit this release. Injection of
CGRP into migraineurs results in delayed headache similar to
migraine. Elevation of CGRP occurs during migraine, resolving
following migraine- specific treatment. Finally, and most importantly,
CGRP receptor antagonists terminate migraine with efficacy similar
to triptans.
Migraine Pathophysiology
• Unclear what they were asking about here.
Buzzwords: trigeminovascular reflex,
peripheral sensitization
•
The pathophysiology of migraine is complex. The first phase of a migraine attack
involves activation of the trigeminovascular reflex, resulting in release of vasoactive
peptides (calcitonin gene-related peptide, neurokinin A, substance P) from trigeminal
afferents supplying dural blood vessels. This produces vasodilation and sterile
inflammation in dural vessels, leading to activation of first-order trigeminal afferents
(peripheral sensitization) and manifested clinically by throbbing head (and neck) pain.
As the attack progresses, second- and third-order trigeminothalamic and
thalamocortical neurons become activated, mediated primarily by nitric oxide and
glutamate transmission, resulting in central sensitization. This is clinically reflected by
cutaneous allodynia.