Headache

Question 1

International Headache Society Classification

Answer 1

1. Primary - without identifiable structural cause
   (migrain, cluster, tension (episodic & chronic), miscellaneous)
2. Secondary - Headaches with underlying structural/metabolic cause
   (brain tumor, meningitis/encephalitis, idiopathic intracranial HTN (pseudotumor cerebri), subarachnoid hemorrhage, giant cell (temporal) arteritis, cerebral vein thrombosis, post-traumatic headache)

Question 2

Temporal Mode of onset/progression of signs/symptoms

Answer 2

• headaches of acute onset (abrupt-onset, rapid worsening)

- headaches of subacute onset (gradual onset, progressive buildup)

Question 3

Pathophysiology Common Among Headaches

Answer 3

-inflammation or physical traction of pain sensitive nerve fibers underlies all types of headaches
Pain sensitive structures:
-dura & meninges at base of brain
-large arteries at base of brain, meningeal arteries
-scalp muscles
-upper cervical muscles
-periosteum of the skull
-facial & head structures/organs (skin, eyes, teeth, nasal sinuses, muscles)

-brain parenchyma has no sensory receptors & is thus INSENSITIVE to pain

Question 4

How is headache pain transmitted?

Answer 4

• centrally via CNs V, VII, IX, X, and the upper cervical nerve roots C2-3
• ophthalmic branch of CN V innervates pain sensitive structures of the anterior/middle fossa and scalp; CN IX & X and cervical nerve roots C2 and C3 innervate the posterior fossa, the cervical muscles & posterior scalp
• pain sensitive nerve fibers synapse in trigeminal nucleus caudalis & dorsal horn of the upper cervical spine
• central pain fibers synapse in VPL & VML nucleus of thalamus and then onto sensory cortex

Question 5

Headache Pain Red Flags

Answer 5

• red flag due to “secondary” etiology
• abrupt onset, recent head trauma, fever, Hx of immunosuppression, altered consciouses, focal neurologic signs/symptoms, new onset >50, neck pain or stiffness, anticoag use, headache progression over days, recently altered cognition, “worst headache of my life”

Question 6

Primary Headaches: Migraine

Answer 6

-chronic neurological disorder causing recurrent headaches w/some or all of the following:
frequently unilateral (may switch sides)
pulsating
moderate to severe intensity
duration of 4-72hr
nausea with or without vomiting
photophobia and/or phonophobia
may be preceded by prodromal phase
may be preceded by an aura in ~20% migraineurs
“triggers” or precipitating factors are frequent
family history

Question 7

Stages of Migraine

Answer 7

• Preheadache (prodrome & aura)
• headache
• post headache
• begin or stop at any stage

Question 8

Migraine Prodrome

Answer 8

in ~40% of migraineurs
-vague constellation of symptoms: mood swings (depression, anxiety, irritability), odd food cravings, malaise or vague feeling of un-wellness, fatigue, muscle aches & stiffness

Question 9

Migraine Aura

Answer 9

-visual disturbance with precedes headache (no more than 60min)
-begin near center of visual field as small gray area with indefinite boundaries
-in minutes, gray expands into horseshoe with bright zigzag lines
-lines grow as a blind (scotoma) area expands and moves outward toward periphery of visual field
(20%)

Question 10

Migraine Epidemiology

Answer 10

• lifetime prevalence ~15-20% of pop.
• women 10-15%, men 5-10%
• begins before age 20
• dec. occurrence after age 25

Question 11

Migraine Genetics

Answer 11

• family history
• polygenic - one loci at 10q23
• familial hemiplegi migraine (dominant gene)

Question 12

Anatomical Substrate for Migraine

Answer 12

• Trigeminovascular System involving CN V1 innervation of pain receptors located in the dura, meninges, and medium/large cerebral arteries & veins that lie on the surface of the brain & above the tentorium
• C2 (back of head)
• CN VII & parasympathetic innervation of Superior salivatory nucleus (vasodilation & other parasympathetic symptoms associated w/migraine reflect central connections b/w pain pathways from CN V & superior salivatory nucleus

Question 13

Brain Stem Nuclei important for Migraine

Answer 13

• magnus raphe, locus ceruleus, dorsal raphe nuclei

- connection b/w trigeminal nucleus caudalis and superior salivatory nucleus

Question 14

Migraine Pathogenesis

Answer 14

-Central Sensitization (brain stem, thalamus)
to central pain (thalamus, cortex, limbic, parasym.)
-Internal, External Triggers (emotional, physical, chemical) to Central Generator (brain stem) or to Aura (cortical)
-Both go to Neurogenic Inflammation (triminovascular system) to central pain

Question 15

Migraine Pathogenesis: Cortical Spreading Depression

Answer 15

• wave of brief neuronal excitation
• prolonged depolarization
• moves across cortex at 2-5mm/min
• brief hyperemia with excitation

Question 16

Migraine Pathogenesis: Migraine Aura

Answer 16

• brief scintillations at leading edge
• move across the visual field that correspond to movement across cortex at 2-5mm/min
• scintillations replaced by scotoma
• CBF measurements in humans during aura show oligemia in affected territory

Question 17

Chemicals Irritate Trigeminal Nerve

Answer 17

2 important neurotransmitters

1) Calcitonin gene related peptide (CGRP)
2) Substance P (SP)
- trigeminal ganglion may function as afferent system and efferent system (sending action potentials from neuron body orthodromically to the sensory nerve terminals where a variety of neurotransmitters chemicals may be released (CGRP and SP into dural & meningeal blood vessels, both vasodilators)

Question 18

Role of CGRP

Answer 18

• mediate neurogenic inflammation & pain in migraine (37 AA peptide)
• CGRP receptors present on dural & cerebral vascular smooth muscle
• potent vasodilator
• causes mast cell degranulation
• serum plasma levels elevated during migraine
• triptans block CGRP release
• CGRP give iv causes migraine like headache

Question 19

Migraine Treatment: Triptans

Answer 19

• sumatriptan first approved for migraine

- agonists at serotonin or 5HT1 receptors, inhibits release of GCRT

Question 20

Migraine Treatment: Gepants

Answer 20

-CGRP antagonists

Question 21

Primary Headaches: Cluster

Answer 21

• Chronic Neurological disorder causing recurrent headaches with some or all of:
• pain always unilateral, frontal, retro-orbital
• unilateral conjunctival infection & rhinorrhea
• unilateral Horner’s syndrome & lacrimation
• Constant, severe, non-pulsing pain
• duration of minutes (3 hrs)
• daily attacks for weeks/months, remission for yrs
• men to women: 4:1
• ~25yrs at onset
• “triggers” are alcohol & tobacco
• rare family history

Question 22

Cluster Headache: Treatment

Answer 22

-acute Rx: nasal oxygen at 8-10l l/min
                subcutaneous Sumatriptan
-Prophylaxis: calcium channel blockers (Verapamil)
                    lithium
                    valproic acid
                    prednsone

Question 23

Primary Headaches: Episodic/Chronic Tension

Answer 23

• chronic neurological disorder causing recurrent headaches with some or all or:
• pain bilateral & bandlike
• not associated with auras, nausea/vomiting, photo or phonophobia
• duration - 3 hrs
• daily attacks < 15 days/month = episodic
• daily attacks > 15 days/month = chronic

Question 24

Episodic/Chronic Tension Headaches: Pathophysiology

Answer 24

-complex & multifactorial

Question 25

Episodic/Chronic Tension Headaches: Treatment

Answer 25

- episodic tension headaches are most common form of headache & rarely prompt an office visit - self medicate with over-the-counter analgesics - chronic tension headaches require a careful & lengthy patient evaluation & followup - best referred to neurologist or headache expert for diagnosis & treatment

Question 26

Secondary Headache: Idiopathic Intracranial HTN

Answer 26

``` -IIH (Pseudotumor Cerebri) Features: -headache of varying character -papilledema -transient visual obscurations -diplopia secondary to CN VI paresis -Tinnitus -constriction of visual fields, enlarged blind spots -Female: Male 9:1 -age 20-45 -overweight, typically by 20% over normal body weight ***emergency, may cause loss of vision*** ```

Question 27

Idiopathic Intracranial HTN Classification

Answer 27

- Primary Idiopathic - cause unidentified - Primary Symptomatic - cause related to underlying metabolic abnormality that alters CSF production or reabsorption - Secondary - cause related to underlying process that physically blocks CSF circulation &/or absorption

Question 28

Idiopathic Intracranial HTN Pathogenesis

Answer 28

-Primary Idiopathic - unknown, inc. CSF production dec. CSF reabsorption -Primary Symptomatic - hypervitaminosis A antibiotics (tetracycline) steroid withdrawal -Secondary - Venous sinus thrombosis Chronic meningitis Chiari malformation

Question 29

Idiopathic Intracranial HTN: Diagnosis

Answer 29

- clinical presentation - MRI & MRV (both should be normal, images r/o masses or venous sinus thrombosis - LP - opening pressure > 250 mm H2O is diagnostic in presence of normal MRI/MRV; pressures b/w 200-250 mm H2O are consistent with Dx but obese people may have CSF pressures normally in this range - Visual Fields - to establish baseline against which to measure treatment success or disease progression

Question 30

Secondary Intracranial Hypertension: Treatment

Answer 30

- (Pseudotumor Cerebri) - weight loss most effective but difficult - reduce CSF production - Acetazolamide, Furosemide - Repeat LPs - Surgical - Optic Nerve Fenestration - Lumbar or ventricular peritoneal shunts - monthly follow up to assure visual system is stable

Question 31

Secondary Headaches: Giant Cell (temporal) arteritis

Answer 31

- autoimmune, systemic vasculitis causing granulomatous infiltration & occlusion of medium/small elastic arteries - Headache: usually unilateral, chief complaint in >70% - point scalp tenderness over temporal artery - visual symptoms - monocular obscurations leading to blindness secondary ophthalmic artery occlusion - associated polymyalgia rheumatica ~50% with jaw claudication, malaise, fever, weightloss, myalgias - Stroke: particularly involving vertebral arteries

Question 32

Giant Cell (temporal) arteritis: lab & Rx

Answer 32

- no single test but ESR inc. in 75% - C-reactive protein also elevated - temporal artery biopsy - may be - in 1/3 because of "skip" lesions - inflammation & multinucleated giant cells in elastic laminae of medium/small arteries - Medical/Neurological emergency (acute onset of monocular blindness) - Corticosteroids should be started immediately with temporal artery biopsy performed ASAP