Headache Flashcards

Question 1

Q

Migraine w/aura

Answer

A

At least two attacks AND…
One or more of the following fully reversible aura symptoms
- Visual, sensory, speech and/or language, motor, brainstem, retinal
At last two out of four characteristics
1. At least one aura symptom spreads gradually over ≥5 minutes, and/or two or more symptoms occur in succession
2. Each individual aura lasts 5-60 minutes
3. At least one aura symptom is unilateral
4. Aura is accompanied by or followed by headache within 60 minutes.
Also TIA has been excluded

Question 2

Q

Migraine w/o aura

Answer

A

At least 5 attacks lasting 4-72 hours (pediatrics 2-7 hours)
Two of the following characteristics:
– Unilateral
– Pulsating
– Moderate/severe
– Aggravated by physical activity
One of the following:
– Nausea +/- vomiting
– Photo- and phonophobia

Question 3

Q

Migraine course

Question 4

Q

Migraine aura

Answer

A

Slow progression over minutes: 5-60 minutes
Migraine aura typically spreads over 5 minutes, and lasts about 5 to 60 minutes, followed by a headache within 60 minutes.

Question 5

Q

Specifying a migraine

Answer

A

Specifying a migraine diagnosis
• Episodic (< 15 days/month) vs. chronic ( > 15 days)
• With or without aura (**NOT complicated migraine**)
– Hemiplegic migraine
– Migraine with brainstem aura
– Retinal migraine

Question 6

Q

Familial hemiplegic migraine

Question 7

Q

Migraine epidemiology

Answer

A

WHO 6th leading cause of disability worldwide
Yearly prevalence 15-18%
Affects 40% of women and 20% of men at
some point in their lifetime
Female:male ratio = 2-3:1

Question 8

Q

Pathophysiology of migraine - vascular?

Answer

A

Way in which vascular component is somewhat incorporated
Migraine Pathophysiology
Activation of TRIGEMINOVASCULAR REFLEX
○ Releases vasoactive peptides (CGRP, Substance P, Neurokinin A) onto dural blood vessels
○ Leads to vasodilation and inflammation of dural vessels
Activation of 1st order trigeminal afferents
(peripheral sensitization-throbbing)
Activation of 2nd and 3rd order neurons in
the thalamus and cortex (central sensitization-cutaneous allodynia)
(2014)

Question 9

Q

Pathophysiology of migraine

Answer

A

Migraine Pathophysiology
Activation of TRIGEMINOVASCULAR REFLEX
○ Releases vasoactive peptides (CGRP, Substance P, Neurokinin A) onto dural blood vessels
○ Leads to vasodilation and inflammation of dural vessels
Activation of 1st order trigeminal afferents
(peripheral sensitization-throbbing)
Activation of 2nd and 3rd order neurons in
the thalamus and cortex (central sensitization-cutaneous allodynia)
(2014)

Question 10

Q

Migraine anatomy

Question 11

Q

Triptans for migraines

Answer

A

MOA: 5HT1B/D agonists: decrease activity in trigeminovascular system (2013, 2020)
- 5HT1B –cranial blood vessels and trigeminal nerve
terminals (B=both)
- 5HT1D –only trigeminal nerve terminals
Avoid in patients with CAD, stroke, vasculopathy, uncontrolled HTN, and if received triptan or ergot derivatives within the last 24 hours.

Question 12

Q

TCAs in migraines

Answer

A

Amitriptyline, Nortriptyline

MOA: Inhibition of serotonin and norepinephrine reuptake. Antagonism of histamine and muscarinic acetylcholine receptors.

Dose: 10-150 mg (1 mg/kg)

SE: Sedation, weight gain, dry mouth, constipation, QT prolongation

Question 13

Q

BBs in migraines

Answer

A

MOA/dosing
Propranolol - Nonselective beta-adrenergic antagonist (penetrates into CNS), 80-240 mg
Metoprolol - Selective β1-adrenergic antagonist (penetrates into CNS), 50-150 mg
Timolol - Nonselective beta-adrenergic antagonist

S/E: Hypotension, fatigue, bronchospasm (contraindicated in asthma)

Question 14

Q

VPA

Answer

A

MOA: Enhances GABA effects, may inhibit glutamate/NMDA receptor- mediated neuronal excitation

Dose: 250-1500 mg

S/E: Teratogenicity, weight gain, hair loss, tremor

Question 15

Q

Topiramate

Answer

A

MOA: Voltage-gated sodium channel antagonism, enhancement of GABA activity, antagonism of AMPA/kainate glutamate receptors

Dose: 25-150 mg

S/E: Weight loss, cognitive slowing, paresthesias, calcium oxalate kidney stones

Question 16

Q

Botox in migraine

Answer

A

Approved for patients with 15 headache days, for 3 months!

Question 17

Q

CGRP antibodies in migraine preventions

Answer

A

-numab: receptor antagonist
Others are all antibody agonists
Receptor antagonist seem to be more for abortive therapy

Question 18

Q

Tx for status migrainous

Answer

A

Status Migrainosus (>72 hours)
Triptans or Dihydroergotamine (DHE) ○ CONTRAINDICATED if triptans or ergot derivatives
used within the past 24 hours ○ Contraindicated in CAD, migraine with motor
weakness, or basilar migraine
Other treatments: IV toradol, IV anti-emetics (prochlorperazine > metoclopramide), steroids
(IV or PO), IV Mg, VPA
Remember that anti-emetics and DHE are QT prolonging agents (2021)

Question 19

Q

CGRP antibody abortives

Answer

A

Ubrogepant (Ubrelvy) and Rimegepant (Nurtec)
- Small molecule CGRP receptor antagonist designed for immediate migraine relief (within 1 hour)

Question 20

Q

Migraine treatment in pregnancy

Question 21

Q

Migraine treatment breastfeeding

Question 22

Q

Pediatric migraine

Answer

A

Characteristics that may differ than adults:
○ Does not require vomiting or throbbing pain
○ May persist for up to 72 hours in children
○ More likely to be bilateral and frontal than unilateral (occipital is rare in children!)
Worsening with physical activity supports migraine
Aura > 60 minutes suggests alternative diagnosis

Abortive Therapy: Ibuprofen! Can use oral triptans.
Preventative Therapy: CHAMPS trial –placebo equivocal to
amitriptyline or topiramate
Cyproheptadine (Periactin) used in younger children (causes weight gain)
Similar approach to adults generally

Question 23

Q

Childhood periodic syndromes: precursor to migraines

Answer

A

Infantile Colic
Benign Paroxysmal Torticollis (2012)
Alternating Hemiplegia of Childhood
Benign Paroxysmal Vertigo of Childhood (2013, 2014, 2015, 2018, 2022)
Cyclic Vomiting
Abdominal Migraine
Ophthalmoplegic Migraine (2012)
Acute Confusional Migraine
Basilar Migraine

Question 24

Q

Benign paroxysmal vertigo of childhood

Answer

A

At least 5 attacks
Episodes of severe vertigo manifest as ataxia, nystagmus, pallor,
vomiting, fearfulness
Occur without warning, and resolve spontaneously in minutes to hours
Normal between attacks
No evidence for another cause (normal MRI, EEG)
Age < 5 and usually resolve by age although may evolve into basilar migraine

Question 25

Q

Benign Paroxysmal Torticollis

Answer

A

Recurrent episodes of head tilt to one side, perhaps with slight rotation, which remit spontaneously.
Occurs in infants and small children, with onset in the first year.

Question 26

Q

Cyclic vomiting syndrome

Answer

A

Episodic attacks, stereotyped in an individual patient, of intense nausea and vomiting lasting from 1 hour to 5 days

Question 27

Q

Acute confusional migraine

Answer

A

Preceded by a mild head bump, first manifestation of migraine, rare (consider other mimics IE seizures)

Question 28

Q

Red flags for secondary HAs

Answer

A

Age > 50 years
History of malignancy or immunocompromised state
Pregnancy
Associated symptoms (fever, weight loss)
Worse with postural changes or Valsava maneuvers
Thunderclap onset

Adult with headache (2020):
HA begins after age 50
Sudden-onset HA
Accelerating pattern of HA
New-onset HA in a patient with cancer, immunosuppressed, HIV
HA with systemic illness (fever, rash, stiff neck)
Focal neurological symptoms of signs (other than typical aura)
Papilledema

Child with headache
Aura > 1h
Persistent neurologic findings/exam between headaches
Occipital headaches
Loss of vision at headache peak
Change in headache pattern
Decline in cognitive function
Changing growth velocity

Headache red flags include systemic symptoms (fever, chills, and weight loss), history of prior cancer or immunodeficiency, focal neurologic signs or symptoms, new headache with onset to peak of seconds to minutes (thunderclap), “first or worst headache,” new- onset headache after age 50 years, precipitation by exertion, strain, or positional changes, increasing headache frequency and severity, and new-onset seizures.

Question 29

Q

Ddx for secondary HAs

Answer

A

Subarachnoid hemorrhage
Intracerebral hemorrhage
Reversible cerebral vasoconstriction syndrome
Cerebral venous thrombosis
Spontaneous intracranial hypotension
Arterial dissection
Pituitary apoplexy
Third ventricular colloid cyst
Pheochromocytoma

Question 30

Q

Secondary HA in pregnancy

Question 31

Q

Giant cell arteritis

Question 32

Q

Spontaneous intracranial hypotension

Answer

A

CSF hypovolemia
Causes of CSF leak:
1. Dural weakness of nerve root sleeves
2. Dural tear from disk herniation
3. CSF-venous fistula

Headache characteristics
– Positional, orthostatic
– Worsened with cough, valsalva
Accompanying symptoms
– Neck stiffness
– Tinnitus
– CN deficits
– Limb parasthesias

Dx/Tx
Lumbar puncture of limited benefit
Brain MRI with and without contrast
CT myelography (slow leaks) vs. heavily T2-weighted spinal MRI/MR myelography
• Treat with blood patch – blind versus targeted

Question 33

Q

Number of days of acute medication use associated with migraine chronification

Question 34

Q

Post traumatic headache

Answer

A

Onset within 7 days of head injury
Similar mechanisms and presentation as migraine although differences shown in fMRI and in reported autonomic symptoms

Question 35

Q

Cervicogenic headache

Answer

A

68% of migraine patients report neck pain
Cervical MRI not that helpful
Other causes of neck pain and headache to consider:
– Cervical dystonia
– Cervical carotid or vertebral artery dissection
– Occipital neuralgia

Treatment of cervicogenic headache
• Anti-inflammatories, Neuropathic pain meds, physical therapy
• Anesthetic blockade (+/- steroid)
– Greater occipital nerve, lesser occipital nerve, third occipital nerve, facet joints (C2/C3), segmental nerve roots

Question 36

Q

CADASIL

Answer

A

Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy
• Autosomal dominant
• Missense mutation in NOTCH3 gene, chromosome 19q13.1

Question 37

Q

MELAS

Answer

A

Mitochondrial Encephalopathy with Lactic Acidosis and Stroke
Mitochondrial inheritance

Question 38

Q

Tension type headache

Answer

A

Most common headache type (prevalence up to 80%)
Mild to moderate, bilateral
Pressure, squeezing, band-like
Rarely with associated symptoms

MOA:
Poorly understood
Thought to be due to muscle tension and myofascial trigger point
Excitation of peripheral nociceptors
Chronic form may be due to central sensitization

Treatment of tension type headaches:
Very few studies
Non-pharmacologic approaches – biofeedback, physical therapy
Acute – acetaminophen, NSAIDs
Preventive – amitriptyline

Question 39

Q

Trigeminal autonomic cephalgias

Answer

A

Unilateral pain (V1) and ipsilateral autonomic symptoms
Restlessness often present
Important to rule out secondary headache and obtain brain MRI with attention to pituitary (and posterior fossa)

fMRI studies of cluster headache and other TACs have shown posterior hypothalamic activation

Long-acting autonomic symptoms with hemicrania is also a long TAC, responsive to indomethacin

Think of it as minutes to seconds, minutes to hour, continuous for table attached

Question 40

Q

Cluster headache

Answer

A

Unilateral orbital/temporal severe pain with autonomic features and migrainous features
Attacks recur at the same time of day (1 to 8 times per day, 15 minutes to 180 minutes)
Episodic 80%, Chronic 20% (unlike PH which is chronic)
Cyclical (4-8 weeks) and Remits ( 6-12 months)
Risk Factors: Males (3 males>1 female), genetic (increased risk in 1st degree relative), smoking

Circannual and 24-hour periodicity
Episodic vs. chronic (if > 1 year without remission or remission < 3 months)

Acute treatment:
– Oxygen: 100% O2 at 12-15 lit/min by non-rebreather mask
– Sumatriptan 4-6 mg SQ or zolmitriptan 5-10 mg intranasal
– Lidocaine nasal spray 4-10%
– GammacoreVNS
Transitional treatment:
– Prednisone taper (e.g. 80 mg x 3 days, 60 mg x 3 days, 50 mg x 3 days, 40 mg x 3 days, 30 mg x 3 days, 20 mg x 3 days, 20 mg x 3 days, 10 mg x 3 days, then stop)
– Ipsilateral greater occipital nerve block with steroids (lidocaine + dexamethasone)
Preventive treatment (start as soon as cluster begins): – Cluster headache preventive therapy should be started immediately at the beginning of a cluster period in episodic cluster. If the cluster periods become chronic (<1 month headache-free period per year) or are significantly increasing in duration, preventive therapy should be continued indefinitely. Preventive therapy should be thought of as “verapamil plus.” Plus includes VPA, Lithium, Melatonin.
– Verapamil – 360-560 mg/d, although can reach 960 mg/d (check EKG!)
– Lithium 600-900 mg/day (aiming for level of 0.6-0.8)
– Gammacore VNS (FDA approved for preventive treatment of episodic and chronic cluster)

Any medication taken by mouth is a poor choice for acute treatment of cluster headache because cluster attacks peak very rapidly, so a fast onset of action is needed to abort the headache quickly. Triptans can be used, but the choice would need to be a formulation with a rapid onset of action, such as sumatriptan subcutaneous injections, sumatriptan nasal spray, or zolmitriptan nasal spray. Sumatriptan subcutaneous needle-free drug delivery system may also be used. Oxygen is very effective as an abortive for cluster and is often used as a first-line treatment. All of the other choices (sumatriptan SC injection, DHE SC injection, zolmitriptan nasal spray, intranasal lidocaine) listed previously, except for frovatriptan, are used for acute treatment of cluster.

Question 41

Q

Hypnic headache

Answer

A

Often presents > 50 years old
Awakens patients ~ 2-4 am
Preventives: caffeine, indomethacin at bedtime
Acute: caffeine, triptans

Question 42

Q

Primary stabbing headache

Answer

A

Common in patients with migraine
Variable location (as opposed to neuralgias) 
Indomethacin responsive, also responsive to gabapentin

Question 43

Q

New daily persistent headache

Answer

A

Distinct onset, often preceded by infection or trauma
Migraine versus tension-type phenotype Often difficult to treat

Begins abruptly, patients will recall exact date it started
Exam and workup up normal
Continuous and unremitting
Persists for more than 3 months
Must rule out secondary causes of headache
Doesn’t have all typical characteristics of other primary headache types.

The diagnosis of NDPH requires a distinct and clearly remembered onset of a continuous and unremitting headache, and it must be present for more than 3 months. Secondary causes or other diagnoses must also be excluded. In general, the pain of NDPH lacks characteristic features and may be migraine-like or tension-type-like, or have overlapping features of both.

Question 44

Q

Trigeminal neuralgia

Answer

A

Brief, lancinating, “electric shock” pain
Usually in distribution of V2 or V3
Often has cutaneous triggers
Get brain MRI for underlying cause (most commonly vascular compression)
Medications (carbamazepine, oxcarbazepine), other treatments include lamotrigine, topamax, and gabapentin
Surgery (microvascular decompression)

The diagnosis of trigeminal neuralgia requires at least three attacks of unilateral facial pain in the trigeminal nerve distribution (one or more divisions), with no radiation outside the boundaries of this territory. Characterization of the pain includes recurrent attacks lasting a fraction of a second or up to 2 minutes, severe in intensity, shooting/electric shock-like/stabbing or sharp, and that could be precipitated by stimuli to the affected area. At least three of those four features are required, and there should be no focal neurologic deficit. Secondary causes or other diagnoses must be excluded. Hypoesthesia or hypoalgesia in the affected trigeminal region suggests axonal damage and trigeminal neuropathy, warranting further diagnostic workup to exclude an etiology.

Question 45

Q

Occipital neuralgia

Answer

A

Must have paroxysms of pain
Can elicit Tinel sign over the nerve
Should be eliminated using nerve block

Question 46

Q

SUNCT

Answer

A

Onset older: 40-70 yo. 1.5 males to 1 female
Stabbing, burning, associated with tearing and eye redness
SHORTEST and MOST ATTACKS: Only last 5-240 sec, 1-100 attacks per day. Often treatment refractory:
Consider carbamazepine, lamotrigine, gabapentin, topiramate, or hypothalamic stimulation. IV lidocaine may work acutely.
Rule out lesions of the skull base, which have been reported
with SUNCT (sellar and posterior fossa tumors)

Question 47

Q

Paroxysmal hemicrania

Answer

A

20-30 year olds, women>men
Frequent attacks: 7-22/day, AT LEAST 8 episodes per day
Short lasting (5 minutes to 45 minutes)
Unilateral, severe, BORING, pulsatile. Around eye w/ ipsilateral autonomic sx’s (V1)
Diagnosis: MRI! Ddx: aneursym, AVM, pancoast tumor, etc

Treatment:
IndometHacin is tx of choice
Defined by response to indomethacin as ppx
No abortive tx
Oxygen and tripans not effective

Question 48

Q

Hemicrania continua

Answer

A

ICHD-3 Criteria
Unilateral, present for >3 months, with at least one of the following:
- Conjunctival injection/lacrimation, nasal congestion/rhinorrhea, eyelid edema, forehead and facial sweating, miosis/ptosis
- Sense of restlessness or agitation, or aggravation of pain by movement“ - Foreign body sensation”, misdiagnosed as migraine or chronic daily headache

IndometHacin responsive

Diagnostics: Most get MRI brain and C-spine
Indomethacin trial is diagnostic (work up to 75mg TID for 1 week)

Question 49

Q

LASH

Answer

A

Autonomic symptoms
○ Overshadow headache and precede headache and continue after headache
○ No continuous “interictal” headache
Lasts several days
Unilateral headache
IndometHacin sensitive

Question 50

Q

Indomethacin responsive trigeminal autonomic cephalgias/headaches

Answer

A

Those with H’s in the name:
Paroxysmal hemicrania
Hemicrania continua
LASH

Also, primary cough headaches, primary stabbing headaches, and for some patients, primary headaches associated with sexual activity.

In order to diagnose or exclude HC and PH, indomethacin should be used in a dose of ≥150 mg daily and increased up to 225 mg daily orally for at least a week (adequate trial generally requires up to 75 mg three times a day, but sometimes a higher dose is required), but for maintenance, smaller doses are often sufficient. It is reasonable to obtain a magnetic resonance (MR) image and magnetic resonance angiogram of the brain with and without gadolinium with thin cuts through the cerebellopontine angle and Meckel’s cave in patients presenting with suspected involvement of the trigeminal nerve, as in HC, trigeminal neuralgia, or any of the trigeminal autonomic cephalalgias.

Question 51

Q

IIH/Pseudotumor Cerebri

Answer

A

Transient visual obscurations, pulsatile tinnitus, VI nerve palsies, papilledema, poor visual acuity
Patient population:
○ Adult overweight woman. Children likely boy with normal body weight
○ Associated with tetracycline, minocycline, vitamin A containing compounds, or steroid
withdrawal in chronic steroid user
Diagnostics: LP with increased ICP (OP>30) without a mass lesion. Also therapeutic acutely!
Treatment: weight loss, acetazolamide/topamax

Question 52

Q

Colloid cysts

Answer

A

“Benign” lesions typically in the 3rd ventricle near/at at the foramen of Monroe
Can cause intermittent hydrocephalus due to its “ball-valve” effect
Results in positional headaches
Sudden death has been reported with this lesion
Avoid LPing!

Question 53

Q

Hemiplegic migraine

Answer

A

At least 2 attacks fulfilling criteria A, B, and C:
A. Aura consisting of both of the following 1. Fully reversible motor weakness 2. Fully reversible visual, sensory, and/or speech/language symptoms
B. At least 2 of 4 characteristics 1. At least 1 aura symptom spreads gradually ≥ 5 min and/or 2 or more symptoms occur in succession 2. Each non-motor aura symptom lasts 5-60 minutes and motor symptoms <72 hours 3. At least one aura unilateral 4. Aura accompanied, or followed within 60 mins by a headache
C. Not accounted for by another diagnosis (TIA/Stroke excluded)

Question 54

Q

Retinal/ocular migraine

Answer

A

Monocular vision loss +/-HA
Unlike visual aura visual deficit in BOTH eyes
2/2 vasospasm of the retinal circulation. Avoid vasospasm inducing medications.
Headache ipsilateral to visual loss

At least 2 reversible attacks lasting <60 min associated with migraine headache

DDx amaurosis fugax

Prevention: calcium channel blockers in addition to
typical migraine ppx +/- ASA

Question 55

Q

Opthalmoplegic migraine

Answer

A

AKA Recurrent Painful Ophthalmoplegic Neuropathy
Repeated attacks of one or more ocular cranial nerves with ipsilateral
headache
CN III most often involved (ptosis, pupillary dilation, exotropia, and diplopia).
Long headache duration (up to a week or more) and a long latent period (up to 14 days) before the onset of ophthalmoplegia
MRI post-GAD can show enhancement of the affected cranial nerve

Question 56

Q

Vestibular migraine

Answer

A

≥ 2 episodes/year of migraine associated with severe, but episodic vestibular symptoms (eg.vertigo)
Work up: Neuroimaging –normal, Vestibular testing (e.g. VNG) – may be abnormal
Likely on spectrum with basilar migraine
DDx: Meniere disease, Vestibular neuritis, Perilymphatic fistula

Question 57

Q

Origins of “sinus-like” signs in migraines, other non-autonomic headaches

Answer

A

Rhinorrhea, lacrimation, sinus pressure, nasal congestion, and conjunctival injection frequently coexist with migraine because of trigeminal nerve (cranial nerve V) cross-activation of the parasympathetics via stimulation of the superior salivatory nucleus (SSN) of the facial nerve (cranial nerve VII). Migraine is frequently misdiagnosed as sinus headache because of these “sinus-like” signs and symptoms.

It is important to re-emphasize the point that rhinorrhea, lacrimation, sinus pressure, nasal congestion, and conjunctival injection frequently coexist with migraine and many other headache disorders such as the others listed due to trigeminal nerve (cranial nerve V) cross-activation of the parasympathetics via stimulation of the SSN of the facial nerve (cranial nerve VII). Migraine is frequently misdiagnosed as sinus headache because of these “sinus-like” signs and symptoms.

Question 58

Q

Tension headache

Answer

A

Diagnosis of episodic tension-like headache requires episodic tension-type headache requires 10 headaches, each lasting between 30 minutes and 7 days. The diagnosis requires at least two of those four features. Neither nausea nor vomiting is present, and there can be only one of either photophobia or phonophobia (either or neither, not both). Secondary causes or other diagnoses must also be excluded. In essence, the criteria for tension-type headache are the complete opposite for that of migraine headache, and this point can be helpful in differentiating between them.

Question 59

Q

Pathophysiology of migraine

Answer

A

1) Activation of hypersensitive “central generator” (it is debated whether the initiating trigger for migraine occurs in the cortex or in the brainstem, or both). →
2) Disrupted ion homeostasis, release of neurochemicals, and transient neuronal dysfunction (cortical spreading depression). →
3) Meningeal blood vessel dilation and activation of trigeminovascular system. →
Release of vasoactive neuropeptides (calcitonin gene-related peptide (CGRP), neurokinins, prostaglandins, substance P, etc.) from activated trigeminal sensory nerves leads to sterile neurogenic inflammation. →
4) Worsening vasodilation, increasing firing of trigeminal afferents and further release of vasoactive neuropeptides causing pain intensification (the vasodilation itself is no longer felt to be the source of pain). →
- This is where you want triptans to intevene-
5) Trigeminal nociceptive afferents carry pain signals to trigeminal nucleus caudalis (TNC) for processing and ascent through thalamus to cortex. →
7) Continuous ascending pain signals activate more neurons, leading to associated symptoms such as photophobia, phonophobia, nausea, and vomiting. →
8) Continuous TNC firing leads to central sensitization (allodynia) if activated pathways are not stopped (triptans have minimal to no effect at this stage; thus, the importance of early triptan administration).

Question 60

Q

Abortive therapy per Chin-Chin, including status migrainous

Answer

A

A triptan combined with a non–steroidal anti- inflammatory drug (NSAID) for early treatment aimed at decreasing neurogenic sterile inflammation. oncurrent administration of NSAIDs with the triptan decreases the neurogenic inflammation, the cause of worsening migraine symptoms. The purpose of the triptan is to reverse meningeal vasodilation, prevent release of vasogenic neuropeptides from the trigeminovascular system, and interfere with return of pain signals to the brainstem.

Intravenous DHE infusion would be reasonable and safe at this point because she has not had a triptan within the last 24 hours. Other intravenous (IV) medications commonly infused with DHE for additional benefit include antiemetics, magnesium, ketorolac, valproate sodium, and steroids. Dihydroergotamine, steroids, promethazine, and ketorolac can all be administered intramuscularly in the absence of infusion capability. Inhaled DHE appears to be as effective as IV DHE with less side effects, although it is not available for clinical use at the time this edition is written.

Question 61

Q

Topamax side-effects

Answer

A

Other side effects to instruct the patient to be aware of when using topiramate include paresthesias in the digits, cognitive slowing, word-finding difficulty, kidney stone formation, and, rarely, acute angle closure glaucoma.

Question 62

Q

CT/LP for SAH

Answer

A

Computed tomographic sensitivity for detecting SAH is highest in the first 12 hours after SAH (nearly 100%), is about 92% sensitive for SAH within 24 hours, and it falls to around 58% by the end of day 5 postbleed.

Lumbar puncture is best performed at least 6 hours after symptom onset and becomes very low yield at 3 weeks. If LP is obtained, an opening pressure should be measured, and the cerebrospinal fluid (CSF) should be sent for cell counts in tubes 1 and 4, protein, glucose, xanthochromia, and gram stain.

Question 63

Q

Triptans MOA

Answer

A

The triptans work as agonists at the serotonin receptor subtypes 5HT-1B and 5HT-1D.

Agonism at 5-HT1B receptors ->constricts the pain-producing intracranial, extracerebral blood vessels in the meninges (as well as 1D effects, B for both)

Agonism at 5-HT1D receptors presynaptically inhibits trigeminal peptide release and interferes with central TNC nociceptive transduction and processing, whereas those of the nucleus tractus solitarius in the brainstem are thought to inhibit nausea/vomiting.

Question 64

Q

Parasympathetic outflow in headaches

Answer

A

Parasympathetic outflow from the SSN of cranial nerve VII leads to activation of lacrimal and nasal mucosal glands.

Parasympathetic fibers travel with the greater superficial petrosal nerve of cranial nerve VII to the sphenopalatine ganglion, synapse, and then travel with the maxillary division (second division; V2) of cranial nerve V to the lacrimal glands. → Lacrimation
Parasympathetic fibers also travel in the lesser superficial petrosal nerve of cranial nerve VII to the otic ganglia.
There is a brainstem connection between the TNC and the SSN causing the trigeminal-autonomic reflex. This reflex is activated by a noxious stimulus applied to the trigeminal distribution. → Rhinorrhea

For example, getting hit in the face with a ball will cause lacrimation and rhinorrhea.

Answer 57

A

Secondary headache disorders have many possible etiologies and are related to an underlying pathologic process. They are associated with an abnormal neurologic examination and/or abnormal diagnostic workup. A family history of brain tumor is not considered a typical “red flag,” although certainly something to keep in mind as you evaluate the patient. A common mnemonic used for headache red flags is SNOOP:

Systemic symptoms (fever, chills, and weight loss) or secondary headache risk factors (HIV and cancer)
Neurologic symptoms or signs (confusion, impaired consciousness, and focal findings)
Older: New-onset or progressive headache, especially >50 years of age (temporal arteritis)
Onset: Sudden, abrupt (thunderclap)
Progression of headache (change in frequency, severity, or clinical features)

Answer 58

A

The duration of a cluster headache is 15 to 180 minutes.

The diagnosis of cluster headache requires at least 5 attacks of severe unilateral temporal, orbital, and/or supraorbital pain lasting between 15 and 180 minutes if untreated. To make the diagnosis, there should be the presence of either agitation or restlessness and/or at least one autonomic sign or symptom on the side of the headache including conjunctival injection, lacrimation, facial sweating or flushing, rhinorrhea, congestion, sense of ear fullness, partial Horner’s syndrome (ptosis and/or miosis), or eyelid edema.

Attacks occur at a frequency ranging from one every other day to eight per day for more than 50% of the time during a cluster cycle. Secondary causes or other diagnoses must also be excluded.

Cluster headache is much more common in men, in contrast to HC and PH which are more common in women.

Answer 59

A

The diagnosis of PH requires at least 20 attacks of severe unilateral temporal, orbital, and/or supraorbital pain lasting 2 to 30 minutes. There should be at least one autonomic sign or symptom on the side of the headache including conjunctival injection, lacrimation, facial sweating or flushing, rhinorrhea, congestion, sense of ear fullness, partial Horner’s syndrome (ptosis and/or miosis), or eyelid edema. The attacks occur more than five times a day for more than 50% of the time. To make the diagnosis, the patient must respond completely to a therapeutic dose of indomethacin. Secondary causes or other diagnoses must be excluded.

Answer 60

A

SUNCT; short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing

SUNA: Short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms

The diagnosis of short-lasting unilateral neuralgiform headache attacks (which include SUNCT and SUNA) requires at least 20 attacks of moderate to severe unilateral head pain in the temporal, orbital, supraorbital, and/or other trigeminal distribution. The duration of the pain ranges from 1 to 600 seconds and may occur as single or series of stabs. The attacks must have a frequency of at least once daily for more than 50% of the time when the disorder is active; however, the attacks generally occur in a very high daily frequency when active. At least one autonomic sign or symptom on the side of the headache is required to make the diagnosis, including conjunctival injection, lacrimation, facial sweating or flushing, rhinorrhea, congestion, sense of ear fullness, partial Horner’s syndrome (ptosis and/or miosis), or eyelid edema. Symptoms should not be attributable to another disorder.

The difference between SUNA and SUNCT is that SUNCT requires both conjunctival injection and lacrimation, whereas SUNA requires only one or neither of conjunctival injection and lacrimation.

aSUNCT and SUNA are rare enough that an MR image without and with contrast should be obtained to rule out secondary causes, especially pituitary tumors or posterior fossa structural abnormalities.

Answer 61

A

The headaches are usually in the occipital region and precipitated paroxysmally by cough, bending forward, and Valsalva maneuvers. When symptomatic, there are other findings of brainstem compression or cervical cord compression, such as ataxia, visual disturbances, hoarseness, dysphagia, vertigo, nystagmus, hearing loss, and cervical myelopathy.

The headache must have developed in temporal relation to the CM1, and/or the headache resolves within 3 months after treatment of the CM1. The headache is precipitated by a Valsalva-like maneuver such as coughing, and/or has an occipital or suboccipital location, and/or the headache lasts for <5 minutes. The headache is associated with symptoms and/or findings of neurologic impairment such cranial nerve, brainstem, cerebellar, and/or cervical spinal cord dysfunction. Other causes or diagnoses must be excluded.

Answer 62

A

Type I involves only extension of the cerebellar tonsils into the foramen magnum - MC, can be acquired

Type II involves extension of both cerebellar and brainstem tissues into the foramen magnum. The cerebellar vermis may be incomplete or absent. It is usually accompanied by a myelomeningocele, most commonly in the lumbar region, and usually results in partial or complete paralysis of the area below that level. The term Arnold-Chiari malformation is specific to type II malformations.

Type III involves herniation of the cerebellum and the brainstem through the foramen magnum and into the spinal cord and is associated with severe neurologic deficits. Part of the fourth ventricle may also protrude through. Rarely, the herniated cerebellar tissue and meninges are present in an occipital encephalocele protruding from the back of the head or the neck.

Type IV is rare, involves an incomplete cerebellum (cerebellar hypoplasia), and portions of the skull and spinal cord may be visible.

The upper limits of normal for tonsillar descent by age are as follows: 6 mm for ages 0 to 10 years, 5 mm for ages 10 to 30 years, 4 mm for ages 30 to 80 years, and 3 mm for ages older than 80 years.

Answer 63

A

An MR image of the brain with gadolinium will often show pachymeningeal enhancement (dura arachnoid enhancement) and downward displacement of the brain and crowding of the posterior fossa due to the sagging and traction of intracranial structures and dura, which may mimic Chiari I malformation.

Answer 64

A

MRI myelography with fat suppression (CSF leak protocol) has come into favor more recently since there is no invasive need to puncture the dura in order to inject a dye or tracer, which can potentially cause a CSF leak if not already present, and there is no need for contrast administration.

Answer 65

A

Idiopathic intracranial hypertension occurs most commonly in young, overweight women. Most patients with IIH have a headache but not all. The headache itself does not have specific characteristics and is frequently described as retro-orbital, frontal, “pressure-like,” or explosive.

They may complain of transient visual obscurations (seconds), graying of vision (especially with straining), diplopia from cranial nerve VI (abducens nerve) palsy, bilateral pulsatile tinnitus, nausea, and vomiting.

Answer 66

A

An early finding of increased intracranial pressure preceding papilledema is loss of spontaneous venous pulsations, although this can also be a normal variant. Disc margin splinter hemorrhages may be seen early also. Eventually, the disc becomes elevated, the cup is lost, and the disc margins become indistinct.

Blood vessels appear blurred as they course the disc. Engorgement of retinal veins leads to a hyperemic disc. As the edema progresses, the optic nerve head appears enlarged and may be associated with flame hemorrhages and cotton wool spots as a result of nerve fiber infarction.

Answer 67

A

Topiramate is used because of its carbonic anhydrase inhibitor effect; it decreases CSF production. Acetazolamide is the classic carbonic anhydrase inhibitor used, unless the patient has a sulfa allergy, which would make topiramate a better choice. Treatment typically begins conservatively with measures such as weight loss, cessation of vitamin A (if toxicity is suspected), weaning steroids, and minimizing other potential risks. If there is no evidence of visual loss, some feel that treatment of the headache alone is sufficient. If there is evidence of visual loss, a carbonic anhydrase inhibitor such as acetazolamide or topiramate should be started. Hydrochlorothiazide is not a typical treatment of IIH.

Procedures should generally be considered when there is progressive visual field defect, visual acuity loss from papilledema, and intractable headache while on maximal pharmacotherapy. Optic nerve fenestration can be done if visual loss is progressive on pharmacotherapy. Serial high-volume LP is no longer recommended because of the short-lasting effect and unnecessary patient discomfort and inconvenience. Procedures performed as a last resort include lumboperitoneal or ventriculoperitoneal shunt.

Answer 68

A

This patient’s history and family history are suggestive of CADASIL. This disorder presents with migraine with aura, stroke or stroke-like episodes, progressive dementia, and other neurodegenerative findings. This is an autosomal dominant disorder most often due to a missense mutation in the NOTCH3 gene, on chromosome 19q13.1 (like APOE4 , although splice site mutations and small in-frame deletions have also been reported. The NOTCH3 gene encodes a transmembrane protein thought to be involved in cell signaling during embryonic development. It can be diagnosed by genetic testing or skin biopsy. Magnetic resonance imaging of the brain will show confluent deep white matter changes. These deep white matter changes characteristically extend to the anterior temporal lobes/poles.

Answer 69

A

Although there are sporadic forms, she likely falls into the category of familial hemiplegic migraine (FHM) given her mother’s history.

There are three types of FHM that are all autosomal dominant with variable penetrance.

FHM1 is linked to chromosome 19p13 (CACNA1A gene), resulting in a defect in P/Q calcium-channel subunit. Additional FHM1 symptoms may include cerebellar involvement, such as gaze-evoked nystagmus or ataxia, also attacks of coma, prolonged hemiplegia, or both, but full recovery is the rule. Transient cerebral edema and cerebral atrophy are less commonly seen.

FHM2 is linked to 1q23 (ATP1A2 gene), resulting in a defect in the A1A2 sodium–potassium ATPase channel. Additional FHM2 symptoms may include recurrent coma, frequent and long-lasting hemiplegia, or seizures with mental retardation. Cerebellar ataxia is not associated with FHM2.

FHM3 is linked to chromosome 2q24 (SCN1A gene), resulting in defects of presynaptic and postsynaptic voltage-gated sodium channels.

Answer 70

A

The diagnosis of hemiplegic migraine requires at least two attacks with an aura characterized by fully reversible weakness and fully reversible sensory, visual and/or speech– language symptoms. Other diagnoses or causes should be excluded, especially conditions such as transient ischemic attack, seizure, and stroke. There must also be at least two of the following features: A headache that occurs with the aura or follows the aura within 60 minutes. One or more aura symptoms that spread over 5 minutes or more and/or two or more symptoms develop in succession. Each motor aura symptom lasts less than 72 hours, and nonmotor aura symptoms last between 5 and 60 minutes. At least one aura symptom has to be unilateral.

Answer 71

A

In this syndrome, patients experience headache as well as other neurologic symptoms such as hemiparesis, ataxia, aphasia, and confusion. Patients have prominent leptomeningeal enhancement. CSF findings are variable but may show a lymphocytic pleocytosis. Leptomeningeal biopsy may show perivascular inflammation. Most often, the etiology is not determined; however, there have been cases seen in association with rheumatoid arthritis or vasculitis. It is essentially a diagnosis of exclusion when other infectious or inflammatory conditions are ruled out.

Answer 72

A

Nummular headache is an uncommon primary headache disorder with pain of variable duration (reported anywhere from seconds to days), but most commonly chronic (75%), in a small well circumscribed area of the scalp without any underlying structural lesion. Patients also often complain of variable sensory disturbances and/or tenderness in the affected area. It was previously named “coin-shaped headache.” The diagnosis of nummular headache requires the presence of head pain felt exclusively in an area of the scalp in an intermittent or continuous fashion. The pain should be round or elliptical with a fixed shape and sharply contoured, measuring between 1 and 6 cm in diameter. There should be no underlying cause.

Answer 73

A

Verapamil

Answer 74

A

Medications with the highest level A (strong) evidence established as effective for migraine prevention: topiramate, divalproex sodium, sodium valproate, metoprolol, propranolol, timolol, and Petasites (butterbur).

Medications with level B (moderate) evidence are established as probably effective for migraine prevention and some of them include amitriptyline, venlafaxine, atenolol, nadolol, feverfew, riboflavin.

Medications with level C (weak) evidence are established as possibly effective for migraine prevention and some of them include candesartan, lisinopril, carbamazepine, nebivolol, pindolol, clonidine, guanfacine, coenzyme Q10, and cyproheptadine.

Some of the medications with level U (insufficient) evidence, which is conflicting or inadequate to support or refute the use for migraine prevention, include verapamil, nicardipine, nifedipine, nimodipine, gabapentin, fluoxetine, fluvoxamine, protriptyline, bisoprolol, and acetazolamide.

There is no evidence for selective serotonin reuptake inhibitors (SSRIs) in the prevention of migraine.

Answer 75

A

The diagnosis of chronic migraine requires that the headache is present on 15 or more days per month for more than 3 months. It must occur in a patient who has had at least five attacks fulfilling criteria for either migraine without aura and/or migraine with aura. Also, on 8 or more days per month for more than 3 months, the patient must have migraine with or without aura and/or believed to have migraine at the onset, relieved by a triptan or ergot derivative. Secondary causes must have been excluded.

At the time this book was being written, the only FDA-approved treatment for prevention of chronic migraine was onabotulinumtoxinA (Botox®). It was approved for this diagnosis in October 2010.

Answer 76

A

The primary mechanism of action of onabotulinumtoxin A is by cleavage of the SNAP25 protein, which is a SNARE (Soluble N- ethylmaleimide-sensitive factor Attachment protein Receptor). The heavy chain portion of the onabotulinumtoxin A neurotoxin binds to the cell membrane of the motor nerve. After binding, it passes through the cell membrane of the motor nerve and into its cytoplasm via endocytosis, where the enzymatic light chain of the onabotulinumtoxin A is activated. Inside the motor nerve, the light chain of the onabotulinumtoxinA cleaves apart the SNAP25 protein, which normally enables vesicles storing acetylcholine to attach to the cell membrane.

Cleaving the SNAP25 prevents these vesicles from fusing with the membrane and prevents the release of acetylcholine into the neuromuscular junction.

Thus, nerve transmissions that normally trigger muscle contractions are blocked. This effect generally lasts for approximately 3 months. New nerve endings sprout and connect to the muscle after the original nerve ending is blocked, renewing the ability of the nerve to cause muscle contractions. Therefore, onabotulinumtoxin A neurotoxin does not permanently alter the neuromuscular junction. Onabotulinumtoxin A effect in chronic migraine may be related to the blockade of the release of neuropeptides involved in the transmission of pain (including substance P, glutamate, and CGRP), theoretically reducing pain sensitization of peripheral nerves.

Answer 77

A

Topiramate has multiple mechanisms of action, including voltage-dependent sodium channel antagonism, enhancement of GABA activity through a nonbenzodiazepine site on GABAAreceptors, and antagonism of AMPA/kainate glutamate receptors.

Answer 78

A

Divalproex sodium primarily increases GABA effects and may inhibit glutamate/NMDA receptor-mediated neuronal excitation. .

Answer 79

A

Propranolol is a nonselective beta-adrenergic antagonist, including at sites in the central nervous system

Answer 80

A

The patient’s headache history is most consistent with hypnic headache. “Alarm clock headache” is an old term, and it is more common in women.

Her neurologic examination is normal, she denies any other neurologic symptoms, and is asymptomatic in between headache attacks, which makes a structural etiology such as brain tumor less likely, although it should still be excluded.

The diagnosis of hypnic headache requires the presence of recurrent attacks of headache developing only during sleep and causing the patient to wake up. The headache must occur on 10 or more days per month for at least 3 months, lasting between 15 minutes and 4 hours after waking. There should be absence of restlessness or cranial autonomic symptoms. Secondary diagnoses should have been excluded.

Hypnic headache typically begins after the age of 50 years and is more common in the elderly rather than the younger. The pain is usually mild to moderate, but severe pain may be seen in some patients. Pain is bilateral in the majority of the cases. There is limited data on optimal treatment, but some of the medications that are more commonly mentioned as possibly effective include lithium, indomethacin, caffeine, and melatonin. Duloxetine has the least evidence of the medications listed.

Answer 81

A

This patient has retinal migraine. It can often be difficult to differentiate between migraine with aura and retinal migraine, but if the visual disturbance is truly monocular, then retinal migraine is the diagnosis. The description of the visual disturbance (positive phenomenon, although negative phenomenon can also occur), the pattern and periodicity, young age, and the association of each event with a headache easily fitting migraine criteria make amaurosis fugax (would be negative visual phenomenon; vision loss such as the classic “lowering of a lamp shade”) very unlikely.

The diagnosis of retinal migraine requires the presence of at least two attacks associated with fully reversible aura consisting of monocular positive and/or negative visual phenomena. These visual phenomena should be confirmed during an attack by a visual field examination and/or the patient’s drawing of a truly monocular field defect. The attacks must also include at least two of the following features: A headache that occurs with the aura or follows the aura within 60 minutes. The aura spreads over 5 minutes or more. Each aura symptom lasts between 5 and 60 minutes. Secondary causes including other causes of amaurosis fugax must be excluded.

Answer 82

A

Tension-type headache is the most prevalent primary headache disorder in the general population, although migraine is the most common primary headache for which patients consult with a physician.

Answer 83

A

Multiple studies including the Women’s Health Initiative Study have shown an association between women who have migraine with aura and increased stroke risk. In women younger than 45 years who have migraine with aura, there is a two-fold increased risk of stroke (not true for migraine without aura).

This risk increases to six- fold with the use of oral contraceptives containing estrogen and nine-fold with the combination of smoking and oral contraceptive use. In women who have migraine with aura who are smokers, estrogen- containing contraception should be considered contraindicated. In women who have migraine with aura, but are not smokers, controversy exists regarding oral contraceptive use given the small but apparent increased risk of stroke.

An interesting study presented at the American Academy of Neurology’s 65th Annual Meeting in San Diego in 2013 looked at almost 28,000 women older than 45 years who were followed up for 15 years. It reported that after high blood pressure, migraine with aura was the second strongest single predictor of heart attack and strokes. It came ahead of diabetes, current smoking, obesity, and family history of early heart disease. Migraine with aura predicted heart disease in women at an adjusted incidence rate of 8% versus an incidence rate of 10% for women with systolic blood pressure spiking at more than 180 mm Hg. T_his increased risk was not seen in migraine without aura_. It is not necessarily thought that migraine with aura causes the stroke, but rather migraine with aura is a marker for young women at a greater risk for cardiovascular disease. However, the reasons for these associations are unclear and likely multifactorial. The combination of traditional vascular risk factors still shows the strongest contribution to cardiovascular disease, so risk factors such as high blood pressure, smoking, diabetes and high cholesterol should be optimized, especially in those with migraine with aura to reduce risk of heart disease or stroke.

Answer 84

A

The American Migraine Prevalence and Prevention Study was a population-based study that followed patients with episodic migraine for up to 6 years for the development of medication overuse headache. It showed that medication overuse can transform episodic migraine to chronic migraine with butalbital compounds (such as Fioricet®) 5 or more days per month, opiates/opioids 8 or more days per month, triptan or combination analgesics 10 or more days per month, and non– steroidal anti-inflammatories (NSAIDs) more than 10 to 15 days per month. Therefore, the medications listed are much more common and likely to be associated with chronic migraine as opposed to an organic structural abnormality such as a brain tumor.

This factor must be eliminated if present and the patients must understand that their headaches will never improve until a weaning detoxification from the overused medications happens, and this can commonly take at least 3 months for significant improvement to occur following detoxification

Answer 85

A

Hemicrania continua, paroxysmal hemicrania, LASH

Answer 86

A

Temporal (giant-cell) arteritis

Answer 87

A

MS, sarcoidosis, Lyme’s disease

Answer 88

A

AD, chasm 19, NOTCH3. mutation

Answer 89

A

AD, chsm 19p13, CACNA1A gene, defective P/Q Ca2+ channel

Answer 90

A

AD, chsm 1q23, ATP1A2 gene, defective A1A2 sodium-channel ATPase channel

Answer 91

A

AD, chromosome 2q24, SCN1A gene, defective pre and post-synaptic voltage-gated Na channels

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