Headache

Primary headaches - Migraines

 

Cortical spreading depression hypothesis

  • Slowly propagating (2-6mm/min) wave of sustained strong neuronal depolarization travelling from posterior to anterior
  • Correlated with EEG and PET hyperactivity followed by hypoactivity

 

    1. Cortical spreading depression
    2. Release of K+, H+, arachidonic acid, prostaglandins, nitric oxide
    3. Activation of trigeminal afferents (meningeal branches of V1)
    4. Local release of CGRP, causing neurogenic inflammation of meninges and mast cell degranulation
    5. Activation of pars caudalis of the trigeminal nucleus
    6. Projections to the PAG and intralaminar nuclei of thalamus (perception of pain)
    7. Activation of superior salivary nucleus, projecting to meningeal blood vessels to release nitric oxide, VIP, Ach, leading to more vasodilation

 

Brainstem generator hypothesis

  • Dorsal raphe nucleus, locus ceruleus for migraine without aura
  • Red nucleus, substantia nigra for migraine with aura
  • These nuclei found to be hyperaemic during and 30 minutes after migraine
  • May allow activation of trigeminal nucleus
  • Theory stems from that activation of PAG can induce migraine-like headaches

 

Migraine without aura

  • At least 5 attacks fulfilling criteria.
  • 4-72 hours (1-72 hours in kids)
  • Two of these:
    • Unilateral (often bilateral in young children)
    • Pulsating
    • Moderate-severe pain
    • Aggravated by activity
  • At least one:
    • Nausea and/or vomiting
    • Photophobia and phonophobia

 

Migraine with aura

  • Recurrent attacks of reversible focal neurological symptoms
  • Symptoms develop over 5-20 minutes, last <60 minutes
  • Headache begins during or within 60 min after aura
  • Can be migrainous or nonmigrainous, or no headache
  • At least 2 attacks with auras
  • Auras can be positive or negative, visual or sensory
  • Aura can also include dysphasic speech disturbance

 

Familial hemiplegic migraine (and sporadic hemiplegic migraine)

  • Autosomal dominant inheritance
  • Migraine with aura with motor weakness
  • Often involve basilar-type symptoms, decreased LOC, fever, confusion, CSF pleocytosis, MRI normal
  • Treatment includes acetazolamide 10-30mg/kg/day or verapamil
  • Sporadic form same clinical symptoms but no family history or known mutation

 

 

FHM1

19p

CACNA1A

P/Q voltage gated Ca channel

50%

Triggered by mild head trauma

Progressive cerebellar ataxia

Episodic ataxia type II, SCA-6

FHM2

1q

ATP1A2

A2 subunit of Na/K pump

20%

Basilar-type migraine

Epilepsy

Alternating hemiplegia of childhood

FHM3

2q24

SCN1A

voltage gated Na channel

 

Subcortical infarcts, small vessel arteriopathy, infantile epilepsy

GEFS+, Dravet

 

Basilar-type migraine

  • Aura symptoms originating from brainstem or bilateral hemispheres, without motor weakness
  • Symptoms include:
    • Dysarthria
    • Vertigo
    • Tinnitus
    • Hypacusia
    • Diplopia
    • Visual symptoms in both temporal/nasal fields of both eyes
    • Ataxia
    • Decreased LOC
    • Bilateral paresthesias

 

Childhood periodic syndromes

 

  • Cyclical vomiting
    • Episodic, stereotypical attacks of intense nausea and vomiting for 1hr-5days
    • Associated pallor and lethargy
    • Vomiting 4x/hr for at least 1hr during attack
    • Normal between attacks
  • Abdominal migraine
    • Midline abdominal pain lasting 1-72 hours
    • Associated with anorexia, nausea, vomiting, pallor
  • Benign paroxysmal vertigo of childhood
    • Attacks of severe vertigo lasting minutes to hours
    • Associated with nystagmus and vomiting
    • Can include unilateral throbbing headache

 

Retinal migraine

  • Attacks of monocular positive or negative visual phenomena
  • Headache fulfills migraine without aura criteria

 

Chronic migraine – migraine occurring >15days/month for >3 months

 

Status migrainosus – debilitating migraine lasting >72 hours

 

Persistent aura without infarction – aura lasting >1 week without radiologic evidence for infarction

 

Migrainous infaction – aura >60 minutes and MRI shows infarct

 

Migraine-triggered seizure – seizure within 60 minutes after migraine aura

 

Primary headaches – Tension-type

 

Tension-type headache

  • Divided into:
    • “Frequent episodic” vs. “infrequent episodic” (<1/mo)  vs. “chronic” (>15d/mo) vs. “probable”
    • With or without pericranial tenderness
  • Most common, but least studied form of headache
  • Bilateral, pressing or tightening, of mild-mod intensity, not affected by activity
  • No nausea. Can have photophobia or phonophobia
  • At least 10 episodes, lasting 30min-7days

Primary headaches – Trigeminal autonomic cephalalgias

 

All forms have prominent parasympathetic autonomic features, with secondary sympathetic dysfunction.

 

Cluster headache

  • Onset age 20-40 years, males > females (4:1), 5% autosomal dominant
  • Postulated pathophysiology is similar to migraine, activation of posterior hypothalamic grey matter
  • At least 5 attacks fulfilling criteria
  • Severe unilateral orbital, supraorbital, and/or temporal pain lasting 15-180 minutes
  • At least one:
    • Ipsilateral conjunctival injection / lacrimation
    • Ipsilateral nasal congestion / rhinorrhea
    • Ipsilateral eyelid edema
    • Ipsilateral forehead and facial sweating
    • Ipsilateral miosis / ptosis
    • Sense of restlessness / agitation
  • Frequency q2d to 8/day, often cluster periods of weeks-months, remission months-years.
  • Episodic cluster – clusters of 7-365 days (usually 14-90 days), separated by >1 month
  • Chronic cluster – cluster >1 year, no remissions or remissions <1mo

 

Treatment:

§         Acute:

o        Oxygen by facial mask 7-10L/min for 15 minutes (70% efficacy)

o        Sumatriptan 6mg SC (75-100% efficacy)

o        DHE nasal spray/IM, zolmitriptan PO, lidocaine

§         Short term prevention:

o        Prednisone 60mg qday, taper after 2-3 weeks

o        Methysergide 1mg/d increase by 1mg q3days until 5mg, then q5days until 12mg

§         Long term prevention:

o        Verapamil 80mg tid, increase 80mg q2weeks

o        Lithium 300mg bid, titrate to high normal levels (600-1200mg qday)

 

Paroxysmal hemicrania

  • Shorter, more frequent, and more in females
  • At least 20 attacks fulfilling criteria
  • Severe unilateral orbital, supraorbital, and/or temporal pain lasting 2-30 minutes
  • At least one:
    • Ipsilateral conjunctival injection / lacrimation
    • Ipsilateral nasal congestion / rhinorrhea
    • Ipsilateral eyelid edema
    • Ipsilateral forehead and facial sweating
    • Ipsilateral miosis / ptosis
  • Frequency ~ 5/day
  • Completely prevented by therapeutic doses of indomethacin
  • Need dose of 150mg PO/PR qday or 100mg IV qday to R/O efficacy (lower dose for maintenance)
  • Episodic paroxysmal hemicrania (see cluster)
  • Chronic paroxysmal hemicrania (see cluster)

 

Treatment:

§         Indomethacin 25mg tid x10 days

o        Increase to 50mg tid x10days

o        Increase to 75mg tid x10days

§         If works, try weening q6months

§         If fails, look for different diagnosis!

 

Short-lasting Unilateral Neuralgiform headache attacks with Conjunctival injection and Tearing (SUNCT)

  • Much shorter attacks with prominent lacrimation and redness of eye
  • At least 20 attacks fulfilling criteria
  • Unilateral orbital, supraorbital, and/or temporal stabbing/pulsating pain 5-240 seconds
  • Ipsilateral conjunctival injection and lacrimation
  • Frequency 3-200/day
  • May be a subform of Short-lasting Unilateral Neuralgiform headache attacks with cranial Autonomic symptoms (SUNA) with other features such as nasal congestion, rhinorrhea, or eyelid edema
  • Refractory to typical headache therapies, but ?highly responsive to lamotrigine 100-200mg/day

Other Primary Headaches

 

Primary stabbing headache

  • Single or series of stabs, predominantly in the V1 distribution
  • Commonly associated with migraine (40%) and cluster headache (30%)
  • Reports of response to indomethacin

 

Primary cough headache

  • Sudden onset headache <30min in association with coughing, straining, or Valsalva
  • Bilateral, in patients >40years
  • Response to indomethacin
  • Can be symptomatic of Chiari I malformation, carotid/vertebrobasilar disease, cerebral aneurysm

 

Primary exertional headache

  • Pulsating headache 5min-48hr brought on during or after physical exertion
  • More in hot weather or high altitude
  • May be prevented with ergots, or treated with indomethacin
  • Must exclude subarachnoid hemorrhage and arterial dissection

 

Primary headache with sexual activity

  • Preorgasmic headache – dull ache in head and neck during sexual activity, increasing with excitement
  • Orgasmic headache – sudden “explosive” headache during orgasm
  • Must exclude CSF leak, subarachnoid hemorrhage, arterial dissection
  • Associated with primary exertional headache and migraine

 

Hypnic headache

  • Dull headache awakens patient from sleep, lasting 15-180 minutes, occurring >15x/mo
  • Begins after age 50 years
  • Must differentiate with intracranial disorders and TACs

 

Primary thunderclap headache

  • Severe headpain, maximal intensity at <1min, lasting 1hr-10d
  • May recur within 1 week
  • Normal CSF and MRI brain
  • Must exclude subarachnoid hemorrhage, intracerebral hemorrhage, CSVT, vascular malformation (aneurysm), arterial dissection, CNS angiitis, benign CNS angiopathy, pituitary apoplexy, colloid cyst, CSF hypotension, acute sinusitis

 

Hemicrania continua

  • Persistent unilateral headache responsive to indomethacin
  • Lasting >3 months
  • Side-locked, daily, continuous, moderate intensity with exacerbations
  • Autonomic features:
    • conjunctival injection/lacrimation
    • nasal congestion/rhinorrhea
    • ptosis/miosis

 

New daily-peristent headache (NDPH)

  • Daily headache within 3 days of onset for >3mo
  • Bilateral, pressing/tightening, mild-mod intensity, not aggravated by activity
  • Can have photophobia, phonophobia, or mild nausea. No vomiting.
  • Usually in a patient without prior headache history

Secondary headaches – attributed to head and/or neck trauma

 

Secondary headaches – attributed to cranial or cervical vascular disorder

Subarachnoid hemorrhage

  • Risk factors: >50, woman, black, smoking, hypertension, heavy alcohol use
  • AVM rupture greatest risk in 3rd trimester
  • Causes:
    • Ruptured intracranial saccular aneurysm (80%)
    • Ruptured intracranial AVM (5%)
  • Can have sentinel headache hours to months prior to bleed
  • Hunt & Hess grading
    • Grade 1 – asymptomatic, minimal headache, mild nucchal rigidity
    • Grade 2 – mod-severe headache +/- CN deficits
    • Grade 3 – drowsiness/confusion, mild focal neuro deficits
    • Grade 4 – Stupor, mod-severe hemiparesis
    • Grade 5 – Coma, decerebrate posturing
  • 15% false negative conventional angiogram
  • Watch for cerebral salt wasting and cardiac stun (high CPK, from catecholamine release)
  •  

Secondary headaches – attributed to non-vascular intracranial disorder

 

Headache attributed to high CSF pressure

  • Idiopathic intracranial hypertension
    • Daily, diffuse, constant pain aggravated by coughing/straining
    • Papilledema, enlarged blind spot, progressive visual field deficit, CN6 palsy
    • Can also have intracranial noises, tinnitus, transient visual obscurations, diplopia
  • Intracranial hypertension secondary to metabolic, toxic, or hormonal causes
    • Endocrine – hypoPTH, hypothyroidism, obesity, Addison disease
    • Medications – Corticosteroids, Lithium, vitamin A, tetracyclines, retinoic acid, bactrim, levothyroxine, growth hormone
  • Intracranial hypertension secondary to hydrocephalus
  • Intracranial hypertension also caused by systemic autoimmune disease – SLE, sarcoidosis, Behçet disease

 

Treatment:

§         Acetazolamide – 1-4g/day (start at 250mg bid)

o        Side effects: distal paresthesias, unpleasant taste, low serum bicarb, allergic rash, anemia, renal stones, sulfa allergy

o        Can use after 20weeks gestation

§         Corticosteroids – 4-6wks in severe visual symptoms

§         Topiramate

§         Intermittent NSAIDs, other migraine prophylactic therapies

§         Optic nerve sheath decompression

§         CSF shunting

 

Headache attributed to low CSF pressure

  • Post-dural puncture headache
    • Worsens within 15 minutes of sitting/standing, improves with lying down
    • Neck stiffness, tinnitus, hypacusia, photophobia, nausea
    • Develops within 5 days of LP, usually resolves within a week or after epidural blood patch
  • CSF fistula headache
    • Occurs after known trauma or procedure
    • MRI pachymeningeal enhancement, evidence of leak on myelography or cisternography
    • CSF opening pressure <60 mmH2O in sitting position
  • Idiopathic low CSF pressure
    • No history of known trauma or procedure

 

Treatment:

§         Bedrest and caffeine for 1-2 weeks

§         Blind blood patch (thoracic/cervical)

§         CT myelograph to ID leak, then patch or surgery

 

Syndrome of transient Headache and Neurological Deficits with CSF Lymphocytosis (HaNDL)

  • CSF pleocytosis with lymphocytic predominance (>15cells/μL), normal cultures and imaging
  • Associated headache and transient neurological deficits
  • Neuro deficits include motor/sensory deficits and aphasia
  • Can also include elevated CSF protein and opening pressure, with papilledema
  • Episodes recur over <3 months

Secondary headaches – attributed to substance or withdrawal

 

Headache induced by acute substance use or exposure

  • Nitric oxide donor
  • Phosphodiesterase inhibitor
  • Carbon monoxide
  • Alcohol
  • Monosodium glutamate
  • Cocaine
  • Cannabis
  • Histamine
  • CGRP

 

Medication overuse headache (MOH)

  • Headache on >15days/mo, regular overuse for >3mo, resolves after 2mo of discontinuation of drug
  • Ergotamine (>10d/mo)
  • Triptan (>10d/mo)
  • Analgesic (>15d/mo)
  • Opioid (>10d/mo

 

Headache as an adverse event attributed to chronic medication

  • Exogenous hormones – contraception or hormone replacement therapy

 

Headache attributed to substance withdrawal

  • Bilateral, pulsating headache associated with withdrawal of regular intake
  • Improves with taking substance or 7 days of withdrawal
  • Caffeine-withdrawal
  • Opioid-withdrawal
  • Estrogen-withdrawal

Secondary headaches – attributed to infection

Secondary headaches – attributed to disorder of homeostasis

 

  • Hypoxia / hypercapnea – altitude, diving, sleep apnea
  • Dialysis
  • Arterial hypertension – pheochromocytoma, preeclampsia/eclampsia, hypertension
  • Hypothyroidism
  • Fasting
  • Cardiac cephalalgia – associated with myocardial infarction, resolves with managment of MI

Secondary headaches – attributed to disorders of cranium, neck, eyes, ears, nose, sinuses, teeth, mouth

Secondary headaches – attributed to psychiatric disorder

 

Cranial neuralgias and facial pain

 

Trigeminal neuralgia (tic douloureux)

  • Classical trigeminal neuralgia
    • Paroxysmal, stereotyped attacks of pain lasting <2min in a division of the trigeminal
    • Intense, sharp, superficial, stabbing
    • Pain can evoke spasm of muscles of face
    • Precipitated from trigger area or trigger factors
      • Washing, shaving, smoking, talking, brushing teeth
    • Often has a refractory period after a paroxysm
    • May be due to compression of trigeminal root or aberrant vessels
    • If bilateral, must consider other etiology, e.g., multiple sclerosis
  • Symptomatic trigeminal neuralgia
    • Same as “Classical” but demonstrable structural lesion found, but no refractory period

 

Glossopharyngeal neuralgia

  • Classical glossopharyngeal neuralgia
    • Same idea as trigeminal neuralgia, but in CNIX distribution
      • Posterior tongue, tonsillar fossa, pharynx, beneath lower jaw, in ear
    • Precipitated by:
      • Swallowing, chewing, talking, coughing, yawning
  • Symptomatic glossopharyngeal neuralgia
    • Aching pain persists between paroxysms
    • Sensory impairment in CNIX distribution

 

 

Nervus intermedius neuralgia

  • Paroxysmal brief pain in depth of ear
  • Trigger area in posterior wall of auditory canal
  • Accompanying lacrimation, salivation, taste changes
  • Associated with VZV
  • Can present like otalgic variant of glossopharyngeal neuralgia

 

Superior laryngeal neuralgia

  • Same but in superior laryngeal nerve
    • Throat, submandibular region, under ear
    • Triggered by swallowing, straining voice, head turning

 

…a bunch more, check the ICHD if interested.

 

 

Tolosa-Hunt Syndrome

  • Rare before age 20 years
  • Episodic orbital pain with paralysis of CN III, IV, VI within 2 weeks
  • Granulomatous infiltration of cavernous sinus / superior orbital fissure / orbit
  • Symptoms resolve within 72 hours of corticosteroids
  • Treatment: Prenisone 60-120mg qday x7-10days
  • 40% patients have relapse

 

Ophthalmoplegic “migraine”

  • Recurrent migrainous headaches with paresis of 1+ ocular cranial nerves (esp. CNIII) within 4 days
  • At least 2 attacks, and no intracranial lesion (MRI may show Gad enhancement of nerve)
  • Headache often lasts 7+ days
  • Not migraine - ? recurrent demyelinating neuropathy

 

Central causes of facial pain

  • Anaesthesia dolorosa
    • painful anesthesia or hypasthesia in trigeminal or occipital nerve from central cause
    • often related to surgical trauma for therapy of cranial neuralgia
  • Central post-stroke pain
  • Facial pain associated with multiple sclerosis

 

Other unclassified headaches

 

Pure menstrual migraine without aura

  • Migraine without aura occurring exclusively on day 1+/-2 of menstruation in at least 2/3 menstrual cycles

 

Menstrually-related migraine without aura

  • Also happens at other times

 

Non-menstrual migraine without aura

  • Migraine without aura in a menstruating woman

 

Migraine aura status

  • 2+ auras per day for >5 days

 

Alternating hemiplegia of childhood

  • Recurrent hemiplegia, progressive encephalopathy, paroxysmal phenomena and mental impairment
  • Onset before age 18 months
  • Paroxysmal phenomena associated with hemiplegia or independently including tonic spells, dystonic posturing, choreoathetoid movements, nystagmus, ocular motor abnormalities, autonomic disturbances
  • Clinical presentation:
    • Phase 1
      • Mild developmental delay
      • Intermittent attacks precipitated by excitement, stress, fatigue
      • Episodic nystagmus, ocular deviation, dystonia, hemiplegia
      • Lasts minutes-days, at least once/month
      • Right side more often affected than left
    • Phase 2
      • Lasts 1-5 years
      • Intensified symptoms, more frequent
      • Developmental regression, persistent neurological deficits
      • May develop choreoathetosis between attacks
    • Phase 3
      • Persistent developmental delay, fixed neurological deficits
      • Decreased in frequency of attacks
  • Normal EEG, MRI, CT, metabolic work-up
  • Outcome:
    • 90% have developmental delay, 50% mild
    • Severity related to age of onset
    • Flunarazine can decrease attack frequency, but does not change outcome

 

Benign paroxysmal torticollis

  • Episodic, self-remitting head tilt lasting mins-days, recurring monthly
  • Associated with pallor, irritability, malaise, vomiting, ataxia
  • Onset in 1st year
  • Can evolve into benign paroxysmal vertigo of childhood, migraine with aura, or nothing

 

Nummular headache

  • Pain in a small circumscribed area of the head without underlying lesion
  • Mild to moderate pain
  • Chronic lasting weeks-months
  • Slight female preponderance

Acute treatments

 

Acetaminophen and NSAIDs

Triptans

  • Serotonin 5HT 1B/D receptor agonists
  • Mechanisms include:
    • 1B - Selective intracranial/extracerebral vasoconstriction (counteracts neurogenic vasodilation)
    • 1D – inhibits trigeminal sensory nerve activation and release of vasoactive neuropeptides
    • 1B/D/F – inhibits neurons of trigeminal-cervical complex
  • Common side effects:
    • Hypertension, vasospasm
    • Atypical sensations (burning, tingling, warmth)
    • Palpitations, syncope
  • Contraindications:
    • Ischemic cardiac, cerebrovascular, peripheral vascular syndromes
    • Vasospastic coronary artery disease
    • Uncontrolled hypertension
    • Basilar or hemiplegic migraine
    • Other meds in 24 hours – ergots (methylsergide, dihydroergotamine) or other triptans
    • Other meds in 2 weeks – MAOIs

Ergots

  • 5HT (non-specific), NE, DA agonists
  • Common side effects:
    • Hypertension, vasospasm
    • Paresthesia, rash, headache
    • Dizziness, anxiety, dyspnea, flushing, diarrhea, increased sweating
  • Severe side effects:
    • Long term use – pleural and retroperitoneal fibrosis
    • Myocardial infarction and stroke

Antiemetics

  • Prochlorperazine and chlorpromazine IV
  • Side effects:
    • Prochlorperazine (Stemetil) is neuroleptic – extrapyramidal symptoms

Opiates

  • Butorphanol nasal spray (atypical opioid)
    • Side effects: dysphoria
  • High risk for dependency and abuse

Status migrainosus therapy

  • Dark, quiet room, IV fluids, sedation
  • IM/IV ketoralac (Toradol) 0.4-1 mg/kg/dose
  • Antiemetics:
    • Metoclopramide (Maxeran) 1-2 mg/kg/dose
    • Chlorpromazine 0.5-1 mg/kg/dose
    • Ondansetron
  • IV DHE 0.1-0.2mg/dose q8h (pretreat with anti-emetic)
  • IV steroids
    • Methylprednisone 1mg/kg/dose
    • Dexamethasone 0.25-0.5mg/kg/dose
    • PO prednisone 40-60mg tapered over 3-5 days

Raskin protocol

  • Metoclopramide 10mg IV q8h x 2-5 days
  • Dihydroergotamine 0.5mg IV q8h x 2-5 days

Prophylactic therapy

 

Drug

Dose

Side effects

ACE inhibitors and angiotensin receptor antagonists

Candesartan

16mg qd

Headache, dizziness, angioedema, hyperkalemia, hyponatremia, leukopenia, rhabdomyolysis

Anticonvulsants

Valproate

500-1500mg

See AEDs page

Carbamazepine

600-1200mg

Gabapentin

600-1200mg

Topiramate

100mg

Antidepressants (TCA, SSRI, MAOI)

Amitriptyline

10-400mg

Dry mouth, metallic taste, epigastric distress, constipation, dizziness, mental confusion, tachycardia, palpitations, blurred vision, urinary retention, orthostatic hypotension, conversion of depression to mania (bipolar), decreased seizure threshold

Beta-adrenergic blockers

Atenolol

50-200mg

Drowsiness, fatigue, lethargy, sleep disorders, nightmares, depression, memory disturbance, hallucination, GI effects, decreased exercise tolerance, orthostatic hypotension, bradycardia, impotence, aggravation of intrinsic muscle disease (myasthenia gravis), teratogenicity, asthma, insulin-dependent diabetes

Propranolol

40-400mg

Calcium channel antagonists

Verapamil

120-640mg

Increase in headache, constipation, dizziness, nausea, hypotension, edema, heart block

Flunarizine

5-10mg

Weight gain, somnolence, dry mouth, dizziness, hypotension, extrapyramidal symptoms, depression

Neurotoxins

Botulinum toxin A

IM q3mo

Anaphylaxis, local and adjacent muscle weakness, dysphagia, dyspnea

Serotonin agonists

Methysergide

 

Retroperitoneal and pleural fibrosis, valvular fibrosis, GI symptoms, edema, flushing, hair loss, weight gain, neutropenia

Others

Riboflavin

400mg qd

Yellow urine

Magnesium

400-600mg

GI effects, arrhythmias

Feverfew

50-82mg

 

Butterbur (Petasites)

50-100mg

 

Coenzyme Q10

100-150mg

 

 

Updated: December 31, 2007

Disclaimer: These are personal study notes. No promises for accuracy or originality.