Managing Headache by Rand Swenson, DC, MD, PhD

1. General
Managing Headache
g g • Head pain arises from pain sensitive structures
–M i
Meninges
– Blood vessels
– Extracranial structures:
Rand Swenson, D.C., M.D., Ph.D. • Sinuses
Professor of Neurology and Anatomy • Upper neck muscles, ligaments
Dartmouth Medical School
Hanover, NH • Eyes
• TMJ
• Dental
– The brain is not sensitive to pain.
General (cont.)
„ Head pain converges
on Spinal Nuc. of
p
Trigeminal.
„ Individual projection
p j
neurons respond to
stimulation of many
cranial structures.
1

2. Interaction between cervical and Sensitization of nociceptors
trigeminal systems
„ C2 nerve terminates in spinal
threshold
th h ld
nucleus of the trigeminal nerve
allodynia
y
hyperalgesia
vasodilation
Anatomy of cerebral vascular General (cont.)
innervation • Innervation of the cerebral blood vessels.
• Trigeminal nerve is sensory…
– Substance P, calcitonin gene related peptide, neurokinin A, maybe
prostaglandins and nitric oxide
– Trigemino vascular system involved in neurogenic inflammation
inflammation.
• Unclear what activates this system..…
• Sympathetic and parasympathetic innervation
– Sympathetic fibers (norepi, neuropeptide Y, prostaglandins),
parasympathetics (acetylcholine, neuropeptide Y).
• Direct innervation from serotonin and norepi containing nerve
fibers
• N
Nerve fib synthesizing nitric oxide
fibers th i i it i id
Girouard & Iadecola. J Appl Physiol 100: 328-335, 2006
2

3. General (cont.)
Central
sensitization
• Serotonin plays a role...
– During migraine blood 5 HT decreases, urine metabolites
increase
– Depletion of 5 HT triggers attack • Central sensitization and neural plasticity
– Intravenous 5 HT relieves attack
– Increased activity of raphe neurons with attacks
definitely contribute
d f l b
– Sleep decreases activity of raphe (and stops attack) • Pain “memory” y
– Decreased 5 HT receptors with age
• “Neurogenic inflammation is clearly a part
Types of headache
yp Types of headache
yp
„Common, benign headache syndromes • Rarely, HA can have serious causes
„Migraine – Eye disorders
„Tension – Brain Tumor
„Cluster – Inflammation of blood vessels
„Cervical
„C i l – Intracranial hemorrhage
„Post traumatic – Ischemic cerebrovascular disease
„Irritation of other cranial structures (sinuses, TMJ, –IIncreased/decreased i t
d/d d intracranial pressure
i l
etc) • Pseudotumor cerebri, Chiari malformation
– Meningitis/encephalitis
/ h l
3

4. A "Bad" Story
Bad "Bad" Signs
Bad
„ Indicates that there may be a serious cause • Meningeal irritation
„ sudden or explosive onset of headache. • Abnormal vital signs
„ a headache that is always in the same place. – Malignant hypertension, fever
„ a headache that awakens from sound sleep. • Papilledema or loss of venous pulsations
„ a headache associated with weakness, numbness, vertigo, loss
of consciousness, vision loss • Unequal pupils
„ changing character of headache in an older patient. • Visual loss
„ new h d h i an elderly i di id l
headache in ld l individual. • Abnormal exam
b l
„ headache associated with fever. – Nystagmus, dysconjugation, ataxia, asymmetry
„ headache in a person with a history of cancer
cancer.
Neuroimaging? A "good story"
g y
• Indications to consider neuroimaging include the
g g • Long history of headaches of a similar nature.
following: unusual, prolonged, or persistent aura; • Slow (not explosive) onset of headaches.
increasing frequency, severity, or change in clinical
features; fi t or worst migraine; basilar; confusional;
f t first t i i b il f i l • Headaches which are not always in the same place
place.
hemiplegic; late life migraine accompaniments; aura • Not loosing function during the attack (no focal
without headache; possibly headaches always on the symptoms other than specific migraine symptoms)
symptoms).
same side; posttraumatic; and when patient or family
and friends request. • No systemic symptoms except nausea.
• Feeling completely normal between attacks.
• Associated symptoms that are like migraine.
4

5. Types of headache
yp User friendly IHS classification
„Common, benign headache syndromes „ Divide the 13 headings into two categories
„ Primary headaches
„Migraine
Migraine and tension- „ Migraine with or without aura
„ Migrainous disorder
„Tension „ Tension type headache (chronic or episodic)
type headaches „ Cervicogenic headache
„Cluster „ Cluster headache
„Cervical
„C i l
comprise the large
p g „ Post traumatic headache
„ Analgesic rebound headache
majority of benign
„Post traumatic
„ Mixed headache syndrome
„ Secondary headache (headache that are symptoms of organic
disease)
„Irritation of other cranial structures (sinuses, TMJ,
headaches
h d h
etc)
Migraine criteria IHS 1.1 Migraine characteristics
g
• Headache with at least two of the following:
• Location of headache
– Unilateral (one side) location
– Pulsing/pounding quality – Many sites
– Moderate or severe • 44% only on one side of the head
– Aggravation by routine physical activity
• 22% are the whole head
• One of the following:
• 14% across th f h d
the forehead
– Nausea
– Light and sound sensitivity
g y
• 13% one side in the front
• Must have had at least 5 similar headaches in the • 4% across the back of the head
past • 2% one side in the back of the head
• It must not be due to other disease • 1% just right at the top of the head
5

6. Migraine symptoms with attacks Classic migraine IHS 1.2
• Migraine accompanied by at least one of the
„Nausea 87% following:
g
„Light sensitivity 82% – Visual
„Vomiting 56% • Scintillating scotoma
g
• Fortification spectra
„Tender scalp 65% • Photopsia
„Diarrhea 16% – Sensory
„May also have:
y • paresthesia
„prior "fluid retention" • Numbness
„nasal "stuffiness" with attack
stuffiness – Other:
• Unilateral weakness
„mood changes common
• Aphasia
Classic migraine characteristics
Migraine activation
• Symptoms usually 5 30 minutes before HA
– Must start within 60 minutes of HA
• Must be < 60 minutes duration
– Spots in front of eyes (often colored spots)
– Fortification spectra
– Wavy lines in vision
– Flashing lights
– Tingling
• Often “marches” over body
marches
– Hemiplegia Cao: Arch Neurol, Volume 56(5).May 1999.548-554
6

7. Migranous disorder not fulfilling other Tension type headache IHS 2.1
criteria (IHS 1 7)
i i 1.7) „ Headache pain accompanied by 2 of the
following:
„ Pressing, tightening or squeezing quality
h l
• Headaches attacks believed to be migranous (nonpulsing)
that do not quite meet the diagnostic criteria for „ Bilateral location
„ Not aggravated by routine physical activity
any of the forms of migraine „ Headache not accompanied by:
• E
Example:
l „NNausea and vomiting
d iti
„ Photophobia and phonophobia (may have one)
– Holocephalic headache of a non pulsing nature „ No evidence of organic disease
g
with nausea and photophobia but not phonophobia „ Fewer than 15 days per month (episodic);
more than 15 days per month (chronic)
Muscle contraction headaches Migraine vs. Tension
g
tension type headaches „ Age: onset <20 years 55% migraine and 30% tension
„ W i symptoms i 60% of migraines and 10% of
Warning: t in f i i d f
„Character: Generalized, nuchal/occipital, tension
bifrontal,
bifrontal cap like or headband Typically
headband. „ Daily: in 3% of migraines and 50% of tension
l f d f
pressure or aching. „ Unilateral: in 80% migraine and 10% tension
„Etiology: May be perpetuated or caused by „ Throbbing: in 80% of migraine and 30% of tension
neck pathology.
p gy „ Vomiting: in 50% of migraine and 10% of tension
g g
„ Family History: in 65% of migraine and 40% of tension
7

8. Migraine vs. Tension Headache Migraine often p g
g progresses to
„Similarities: tension type headache
„ Migraine may progress to tension headache
„ Migraine and tension similar in that:
„Neck muscle contraction found in both
„Neck muscle contraction and pain common in prodrome of both
„ Cephalic hyperemia attends HA in both
„ Increased prevalence of epilepsy in both
„ Low platelet serotonin occurs in both
„ Psychological profiles of patients indistinguishable
„ Both disorders respond to similar medicines (Elavil, ergonovine
and inderal)
“Per headache” treatment
Per headache “Per headache” treatment
Per headache
• How most patients manage their HA • 81% of migraine patients take
• “Step care” medication
– Escalating levels of treatment • Only 32% are using
– Relaxation prescription medication
– Herbal
• 60% take over the counter
– Physical
– Analgesics
medication
• Earlier is better
Migraine Sufferer Identification and Impact -on-life Study
on-
8

9. “Per headache” treatment
„Potential problems with step care
„Analgesic rebound is a common condition in
patients with frequent headache
„Especially with narcotics butalbital acetaminophen
narcotics, butalbital,
and caffeine containing combinations
„Many medications have unpleasant side effects
„GI effects NSAID
„Sedation narcotics, b lb l antiemetics
d butalbital,
„Triptans chest pain/tightness, rare MI
“Analgesic rebound headache
Analgesic rebound”
„ Usually daily, diffuse and bilateral with superimposed
migraines periodically
i i i di ll
„ Physical and mental exertion worsens
„ Often with HA in AM or awaken with it
„ High coincidence of restlessness, nausea,
forgetfulness, asthenia, depression
„ Tolerance to abortive medication
„ No response to preventative migraine medication
Mathew NT. Neurol Clin NA 1990;8:903-912
1990;8:903-
9

10. Frequency of misdiagnosis Migraine is expensive
• Only 56% of migraineurs know that they have migraine. In a recent study,
y g y g
sinus headache (39%), tension type headache (31%), and stress
y,
„Average costs in 18 months
„$2,187 in medical bills
headache (29%) were common self reported diagnoses among
migraineurs (subjects could list more than one probable diagnosis).
„For doctors visits, emergency room visits,
– Diamond S., Bigal M.E., Silberstein S., et al: Patterns of diagnosis and acute and preventive treatment for migraine in the
United States: results from the American Migraine Prevalence and Prevention study. Headache 47. 355-363.2007
• In a study of 2991 patients who had a history of self described or p
hospitalizations
physician diagnosed sinus headache, 88% were diagnosed as f f fulfilling
migraine (80% of patients) or migrainous criteria (8% of patients)
– Schreiber C.P., Hutchinson S., Webster C.J., et al: Prevalence of migraine in patients with a history of self reported or
„$371 in bill for drugs
„$2,558
„$2 558 total bill
physician diagnosed “sinus” headache Arch Intern Med 164 1769 1772 2004
sinus headache. 164. 1772,
l
Clouse & Osterhaus. Ann Pharmacother 1994;28:659-664
Lost productivity
Migraine impact • Stewart and colleagues mailed a questionnaire to
193,477 participants in the American Migraine
„E
Economic productivity
i d ti it Prevalence and P
P l d Prevention study.
ti t d
„ 89% of migraine suffers worked at half or less of their usual • The average lost Productive Time (LPT) was 1.8 hours for
productivity for an average of 6 days a month headache and 2 8 for all health related causes
2.8
„ 56% missed work at an average rate of 2.2 days a month • 76.5% of the headache related LPT was explained by
„ Estimated lost labor costs (per month) reduced performance (ie, presenteeism).
„ $572 per working male and • The 29% of migraine cases with 11+ headache d/mo
„ $300 per working female accounted for 49% of overall LPT; the 19% of those with
pain score of 9 to 10 on a 0 to 10 scale accounted for
33% of the overall LPT.
– Stewart W F Wood G.C., Razzaghi H., et al: Work impact of migraine
W.F., GC H
headaches. J Occup Environ Med 50. (7): 736 745.2008
Osterhaus et al. Pharmacoeconomics 1992;2:67-76
10

11. Difficult HA and Migraine is an Steps in migraine treatment
opportunity
„ Diagnosis
• Underserved population „ Establish good doctor patient relationship
• Underdiagnosed population „ Educate patients and families
p
• A population for which conventional medical Tx is „ Reassure patients
ineffective or even counterproductive
„ Ask patients to keep daily log of HA
• A population that most physicians don’t want to see
„ Explore non pharmacologic treatments
and/or are inadequately prepared to see
„ Treat aggressively until adequate response
• Analgesic rebound or analgesic overuse headache is
common „ Periodically re evaluate treatment
• Oral medicine often not effective during attack
Migraine treatment
g Migraine Precipitants
• Modification of trigger factors • Stress important…
• Stress management – but often in "let down" period..
• Sleep hygiene • Pregnancy may get better or worse
• "Per headache" treatment? • Low dose OC's
• Prophylactic therapy
p y py – Better than high dose, still risky
– Spinal manipulation • 60% linked to menstruation, 14% exclusively
– ?Acupuncture • Common factors: lack of sleep, hunger, head trauma,
– Omega 3 oils, antioxidents, magnesium, B vits, herbal excessive sleep, altitude, high vitamin A, drugs, cold food,
• Behavioral therapy
py eye strain, odors (perfume, smoke), fluorescent lights,
allergies, glare.
11

12. Migraine Precipitants (cont.) Sleep Disorders
„Overnight headaches or headaches upon arising
• Common foods: Chocolate (50%), alcohol/wine
(40%), dairy products (30%), citrus (30%), Beer reflected sleep disturbance in 55% of patients.
patients
(15%), fried foods (10%), pork (10%), onions (9%), „Treatment of sleep disorder improved headache
tea/coffee (7%)
t / ff (7%), seafood (5%).
f d (5%) in all of this 55% (and stopped it in 65%).
• Occasionally, salt, aspartame, nitrates. „ Penzien DB. Rains JC. Andrasik F. Behavioral management of recurrent
• Caffeine withdrawal. headache: th
h d h three d d of experience and empiricism. A li d
decades f i d ii i Applied
Psychophysiology & Biofeedback. 27(2):163 81, 2002.
Neck and TMJ contributes to HA Cervicogenic headache
„ Strong attachments to the dura
• May be associated with temporomandibular joint
y p j matter in the C1 Occiput level
pathology and upper cervical „ Interaction with C2 nerve root
• Occipital neuralgia: may be from direct injury or from
p g y j y
spasm of trapezius and semispinalis muscles.
– Produces an ipsilateral aching, burning or shooting p
p g, g g pain.
Occasionally with electrical or lightning sensations in occiput
• Convergence in spinal nucleus of the trigeminal
12

13. Rectus capitus posterior minor Dural attachments
„ This has strong dural attachments
in the C1 Occiput level
Prophylaxis
op y a s
• This is especially useful if headaches are
Dural frequent
attachments – U ll 2 4 severe episodes per month
Usually i d th
– Especially if HA medication 2 or more days/wk
• Chiropractic treatment was comparable (and
much longer lasting) than a common migraine
g g) g
prophylactic medication.
13

14. Migraine and Manipulation Migraine and Manipulation
„ Nelson, et al. JMPT 21:511 519, 1998
„ Spinal manipulation versus amitriptyline and the combination of
p p py „ PARTICIPANTS: 175 patients with migraine (>1/mo)
both for the prophylaxis of migraine. „ INTERVENTIONS: 2 mo., 16 TX max.
„ Prospective, randomized parallel group comparison. „ RESULTS: treatment group (n=83) showed statistically
„ 4 week baseline, 8 weeks of treatment and 4 week f/u significant improvement in migraine frequency (P <
f f (
.005), duration (P < .01), disability (P < .05), and
„ 218 patients with migraine. Used headache index score medication use (P< .001)
001)
from daily headache diary. „ 22% of treated patients had > 90% reduction
„ Reduction in headache score of 49% for amitriptyline 40%
for manipulation and 41% for combination.
„ In the 4 week post treatment period, reduction from baseline
was 24% for amitriptyline, 42% for chiro and 25% for both.
Tuchin PJ. Et al JMPT. 23:91-5
Tension Type HA
yp Indications for preventive TX
• 126 patients >3 months with at least 1 episode per week of • Indications for preventive treatment are as follows:
tension type headache. Randomized to group 1 (spinal – Headaches significantly interfere with the patient's daily
manipulation, moist heat and OTC's) or group 2 (amitriptyline and routine despite acute treatment;
OTC's as needed). There was no pretreatment difference in – Acute medications are contraindicated, ineffective, or
headache frequency, intensity, OTC use or functional status.
frequency intensity status overused,
overused or have intolerable side effects;
• Treatment Group 1 was treated twice per week for 6 weeks, – Frequent migraines (two or more attacks a week);
group 2 was seen a baseline and 6 weeks later. – Uncommon migraine types (hemiplegic, basilar,
(hemiplegic basilar
• Results 4 weeks after treatment group 1 had >30% improvement prolonged aura, or migrainous infarction);
in intensity, frequency and OTC use and 16% improvement in
y q y p – Cost of acute medications is significantly greater than the
functional status. Group 2 improved <6% in all measures. cost of preventive medication;
– Patient preference.
Boline et al.
14

15. HA Prophylaxis
p y Principles of preventive TX
• Start with a low dose and increase it slowly, depending on the
„ Decision to use preventative medicines is based on response and side effects.
severity,
severity frequency and the availability of effective • Each treatment should be given a trial of 2 to 3 months at adequate
treatments doses.
„ Common medicines used for this purpose include: • Overused medications should be discontinued or tapered
„ Heterocyclic antidepressants (depending on the drug). They may be causing rebound headache
„ Beta blockers and can decrease efficacy of preventive treatment
„ Calcium channel blockers • The patient should keep a HA diary to monitor his or her HA.
„ Seizure medicines: Valproate, Topiramate, Neurontin, etc • The clinician should educate the patient about the rationale for
treatment and possible side effects and should address the patient's
patient s
expectations for treatment. Many patients want a complete cure,
and although this is certainly understandable, it is usually not
possible.
possible
When to stop preventive TX? Magnesium
• Only RCT trial has been performed to investigate migraine • 81 migraineurs (3.6 attacks/mo.)
after preventive treatment discontinued. – Baseline=4 weeks; randomized to 600 mg ( mmol) Mg2+
; g (24 ) g
– Patients treated with topiramate for 6 months were randomized (trimagnesium dicitrate) daily for 12 weeks or placebo
to continue or switch to placebo for 6 months. – In weeks 9 12, attack frequency was reduced 41.6% in the
– Discontinuation “…was associated with persistent benefits
was Mg2+ group and 15 8% in the placebo group (compared to the
15.8%
compared with values before treatment, although numbers of baseline; p < 0.05)
migraine days were higher and quality of life was lower in – Days with migraine and drug consumption also decreased
g
patients who di
ti t h discontinued t i
ti d topiramate use th i th
t than in those who
h significantly w/ Mg2+
continued treatment. Patients should therefore be treated for 6
months, with the option to continue treatment to 12 months in – Duration and intensity of the attacks and the drug
some patients, particularly those whose migraine frequency consumption per attack tended to decrease (N/S)
decreased substantially with topiramate.” • Diarrhea (18.6%); gastric irritation (4.7%)
• Diener H.C., Agosti R., Allais G., et al: Cessation versus continuation of 6 month migraine preventive
therapy ith
therap with topiramate (PROMPT) a randomised do ble blind placebo controlled trial Lancet
(PROMPT): randomised, double blind, trial.
Neurol 6. 1054 1062, 2007
Peikert, eta al. Cephalalgia. 16(4):257-63, 1996
15

16. Magnesium Magnesium
• 69 patients (2 6 common migraines/mo for >2 years)
• Randomized to 10 mmol Mg2+ bid or placebo
• 40 patients with migraine without aura
i ih i i ih
• 4 week baseline period; 12 weeks of Tx
• 600 mg/day of oral magnesium citrate per day versus
• 10 responders (>50% fewer HA) in each group (28.6%
(28 6%
placebo w/TX; 29.4% w/ placebo)
• Significant decrease in migraine attack frequency and – 45.7% of patients in the magnesium group reported mild
severity. adverse events like diarrhea (23.5% w/ placebo).
– Koseoglu et al. The effects of magnesium prophylaxis in • Study stopped early D/T no effect, but poorly absorbed
migraine without aura. Mag Res. 2008;21:101–108 form of Mg2+
Pfaffenrath, et al. Cephalalgia. 16(6):436-40, 1996
Magnesium Mitochondria
• 86 children (3 to 17) • Mitochondrial dysfunction has been speculated to play a role in
migraine pathophysiology
– 4 week history of at least weekly moderate to severe
weekly, • Koo et al. Mitochondrial encephalomyopathy, lactic acidosis, stroke like episodes (MELAS): Clinical,
migraine radiological, pathological, and genetic observations. Ann Neurol. 1993;34:25–32.
• Lanteri Minet & Desnuelle. Migraine and mitochondrial dysfunction. Rev Neurol. 1996;152:234–238.
• Randomized to magnesium oxide (9 mg/kg p day by
g ( g g per y y
• Mi i
Migraineurs h
have reduced mitochondrial phosphorylation potential
d d it h d i l h h l ti t ti l
mouth divided 3 times a day with food) or placebo for
in between headaches
16 weeks • Montagna et al. 31P magnetic resonance spectroscopy in migraine without aura. Neurology.
1994;44:666–669.
1994 44 666 669
• Significant decrease in HA f
f d frequency with Tx (P =.0037)
h ( ) • Bresolin et al. Muscle mitochondrial DNA deletion and 31P NMR spectroscopy alterations in a migraine
but not placebo (P =.086) patient. J Neurol. 1991;104:182–189.
• Magnesium oxide group had significantly lower • This might reduce the threshold for migraine attacks. Rationale for
attacks
headache severity (P =.0029) supplements that enhance mitochondria
– Riboflavin, CoQ10, and alpha lipoic acid.
• Sparaco et al. Mitochondrial dysfunction and migraine: Evidence and hypotheses. Cephalalgia.
2006;26:361–372.
Wang, et al. Headache. 2003 Jun; 43(6): 601-10
16

17. Riboflavin Riboflavin
• Riboflavin, also known as vitamin B2, is a precursor for
flavin mononucleotides that are cofactors in the Krebs • A recent pharmacogenetic study demonstrated that
cycle.
cycle It is essential for membrane stability and the riboflavin may be more effective in the treatment of
maintenance of energy related cellular functions. migraine patients with non H mitochondrial DNA
• One well designed RCT evaluating the use of riboflavin as a haplotypes.
migraine prophylactic agent. • Riboflavin is effective in deficiencies of the electron
• Daily use of 400 mg riboflavin for 3 months resulted in a transport chain complex I but not in isolated complex IV
50% reduction in attacks in 59% of patients, as compared
deficiency
with 15% for placebo.
– This haplotype is more common in Northern Europeans
• Two minor adverse reactions, diarrhea and polyuria, were
d d h d l
• DiLorenzo, et al. Mitochondrial DNA haplogroups influence the
reported in the treatment group. therapeutic response to riboflavin in migraineurs. Neurology.
• Schoenen J Jacquy J Lanaerts M. Effectiveness of high dose riboflavin in migraine
J, J, M 2009;72:1588–1594.
2009 72 1588 1594
prophylaxis. Neurology. 1998;50:466–470.
CoQ10 Coenzyme Q10
• CoQ10 is an endogenous enzyme cofactor made by all cells in the body, functioning to
promote mitochondrial proton electron translocation. • CoQ10 (3 x 100 mg/day) v. placebo
• An open label study of 31 patients with migraine used 150 mg daily of CoQ10 for 3 • 42 migraine patients
months, 61% had at least a 50% reduction in migraine days without significant
adverse events. • Double blind, randomized, placebo controlled trial
– Rozen TD, Oshinsky ML, Gebeline CA, et al. Open label trial of Coenzyme Q10 as a migraine preventive. Cephalalgia.
2002;22:137–141.
• A small randomized controlled trial was conducted in which the treatment group • CoQ10 was superior to placebo for attack frequency
frequency,
received 100 mg of CoQ10 3 times daily. headache days and days with nausea in the third
• CoQ10 significantly decreased attack frequency, headache days, and days with
nausea. treatment month and well tolerated
– Sandor PS, DiClemente L, Coppola G, et al. Efficacy of coenzyme Q10 in migraine prophylaxis: a randomized controlled trial.
Neurology. 2005;64:713–715. – 50% responder rate for attack frequency was 14.4% for
• CoQ10 levels were measured in a study of 1550 pediatric patients (mean age placebo and 47.6% for CoQ10
13.3±3.5 ) i h frequent h d h and f
13 3 3 5 y) with f headaches, d found to b b l the reference range in
d be below h f i
32.9%.
• Supplementation with 1 to 3 mg/kg/d of CoQ10 in liquid gel capsule formulation
resulted in an improvement in total CoQ10 levels headache frequency and degree of
levels,
headache disability.
– Hershey AD, Powers SW, Vockell AB, et al. Coenzyme Q10 deficiency and response to supplementation in pediatric and Sandor, et al. Neurology 64(4):713-5, 2005
adolescent migraine. Headache. 2007;47:73–80.
17

18. Alpha lipoic acid Fatty acids
• Alpha lipoic acid (also known as thioctic acid) enhances • Eicosapentaenoic acid (EPA), may also be useful in the prevention
mitochondrial oxygen metabolism and ATP production. of headaches. Small studies suggest that HA severity & frequency
• One placebo controlled RCT can b reduced b adding di t
be d d by ddi dietary EPA possibly l
EPA, ibl lowering
i
prostaglandin levels and serotonin activity.
• Fifty four patients received either 600 mg alpha lipoic acid or
– Werbach M. Nutritional Influence on Illness: A Sourcebook of Clinical
placebo daily for 3 months
months. Research. Tarzana, CA: Third Line Press, Inc; 1988.
R h T CA Thi d Li P I 1988
• Although there was a clear trend for reduction of migraine • Omega 3 fatty acid supplementation also associated with a
frequency after treatment with alpha lipoic acid, the result was
q y p p , positive outcome in the treatment of mood disorders.
not significant. – Stahl LA, Begg DP, Weisinger RS, et al. The role of omega 3 fatty acids in mood
disorders. Curr Opin Investig Drugs. 2008;1:57–64.
• This result was attributed to the fact that the study was • Although the FDA has not established a recommended daily
underpowered. However, within group analyses did show a allowance for EPA, a dose of 600 mg/d in 3 divided doses has been
significant reduction in attack frequency, headache days, and suggested for headache prevention.
headache severity in the treatment group. – Dupois S A comprehensive approach to treatment of intractable headaches
S. headaches.
– Magis D, Ambrosini A, Sandor P, et al. A randomized double blind placebo controlled trial Townsend Lett Doctors. 1990;88:740–744.
of thioctic acid in migraine prophylaxis. Headache. 2007;47:52–57.
Fatty acids Butterbur
• Eicosapentaenoic acid (EPA), may also be useful in the prevention
of headaches. Small studies have suggested that headache • Petasites is thought to act through calcium channel regulation
severity and f
i d frequency can b reduced b adding EPA to the di
be d d by ddi h diet, and inhibition of peptide leukotriene biosynthesis Leukotrienes
biosynthesis.
possibly by lowering prostaglandin levels and serotonin activity. and other inflammatory mediators may have a role in the
– Werbach M. Nutritional Influence on Illness: A Sourcebook of Clinical inflammatory cascade associated with migraine.
Research. Tarzana, CA: Third Line Press, Inc; 1988. • Although the butterbur plant itself contains pyrrolizidine
• Omega 3 fatty acid supplementation has also been associated alkaloids which are hepatotoxic and carcinogenic, these
with a positive outcome in the treatment of mood disorders
disorders. compounds are removed in the commercially available
p y
– Stahl LA, Begg DP, Weisinger RS, et al. The role of omega 3 fatty acids preparations. [Petadolex]
in mood disorders. Curr Opin Investig Drugs. 2008;1:57–64. • Placebo controlled RCT using 50 mg of butterbur twice daily,
• Although the FDA h not established a recommended d il
Al h h h has bli h d d d daily showed a significantly reduced number of migraine attacks and
allowance for EPA, a dose of 600 mg/d in 3 divided doses has migraine days per month.
– Grossman M, Schmidrams H. An extract of Petasites hybridus is effective in the prophylaxis of migraine. Int J
been suggested for headache prevention. Clin Pharmacol Ther. 2000;38:430–435.
– Dupois S. A comprehensive approach to treatment of intractable
headaches. Townsend Lett Doctors. 1990;88:740–744.
18

19. Petasites (butterbur) Petasites (butterbur)
• Three arm, parallel group, randomized trial „ 4 week baseline phase
– Petasites extract 75 mg and 50 mg bid, or placebo in 245
„ 33 patients randomized to Tx (50 mg butterbur twice
patients with migraine a day) or placebo (n=27)
„ Mean attack frequency per month decreased from 3 4 3.4
• Over 4 months of treatment, migraine attack
h f i i k
at baseline to 1.8 after 3 months (p = 0.0024) with TX
frequency was reduced by 48% for Petasites extract and from 2.9 to 2.6 with placebo group (n.s.).
75 mg bid (p = 0 0012 vs placebo), 36% for Petasites
0.0012 placebo)
„ > or =50% improvement: 45% in the Tx group and 15%
extract 50 mg bid (p = 0.127 vs placebo), and 26% for in the placebo group.
the placebo group
„ Butterbur was well tolerated.
• Potential carcinogen
• Lipton et al. Neurology 63(12):2240 4, 2004
Lipton, al Neurology. 63(12):2240-4
Diener, et al. European Neurology 51(2):89-97, 2004
Butterbur Feverfew
„ The use of feverfew (Tanacetum parthenium) for migraine
• A multicenter prospective open label study 94 of prophylaxis was assessed in a randomised, double blind,
butterbur in 109 children and adolescents with placebo controlled crossover study.
l b t ll d t d
migraine resulted in 77% of all patients reporting a „ 72 volunteers were randomly allocated to receive either one
reduction in migraine frequency of at least 50%. capsule of dried feverfew leaves a day or matching placebo for
– Pothmann R, Danesch U. Migraine prevention in children and adolescents: results of an open study with four months and then transferred to the other treatment limb for
a special butterbur root extract. Headache. 2005;45:196–203.
a further four months.
• Butterbur is well tolerated and no serious adverse „ There was a reduction in the mean number and severity ofy
events occurred. The most frequently reported adverse attacks in each two month period, and in the degree of
reactions were mild gastrointestinal events, vomiting; duration of individual attacks was unaltered.
predominantly eructation (burping)
(burping). There were no serious side effects
effects.
„ Murphy et al. Lancet. 2(8604):189 92, 1988 Jul 23.
19

20. Feverfew Combinations
• RCT of extract of feverfew (MIG 99, 6.25 mg t.i.d.) vs. • RCT of riboflavin 400 mg/mg 300 mg/feverfew 100 mg v. placebo
placebo (25 mg riboflavin)
• 170 migraineurs; 4 week baseline; treated for 16 • 49 migraineurs: 1 month run in; 3 month trial
weeks • No difference between active and "placebo" groups
– 42% of Tx and 44% of placebo achieved >50% reduction (no difference).
• Migraine frequency decreased by 1.9/mo (from 4.76) – No significant difference in change in mean number of migraines,
in months 2 & 3 with Tx (decreased by 1.3 w/placebo) migraine days, migraine index, or medication doses
(P=0.0456) • Both groups had significant reduction (from baseline) in number
• No evidence of more adverse effects compared to of migraines, migraine days, and migraine index.
placebo • Thi effect exceeds prior placebo reports
This ff t d i l b t
– Diener HC, Pfaffenrath V, Schnitker J, et al. Efficacy and safety of 6.25 mg tid feverfew CO2
extract (MIG 99) in migrane prevention—a randomized, double blind, multicenter, placebo
controlled study. Cephalalgia. 2005;25:1031–1041.
– Pfaffenrath, et al.(Cephalalgia. 22(7):523 32, 2002) believe this may only work in
patients with frequent migraine (4 or more/mo) Maizels, et al. Headache. 44(9):885-90, 2004
5 Hydroxytryptophan 5 Hydroxytryptophan
„ 48 elementary and junior high school students with „ A double blind cross over study in 31 patients with
chronic primary headache, comparing 400 mg per day of
p y , p g gp y
recurring headache and sleep disorders were selected
L 5 HTP to placebo.
for this study.
„ Over two months L 5 HTP proved to be more effective than
„ A double blind cross over trial with placebo
blind, placebo i reducing both headache frequency and severity,
l b in d i b th h d h f d it
confirmed benefit of L 5 hydroxytryptophan for but the difference was not statistically significant.
headache and some sleep disorders, in particular
disorders „ Greater than 50% average reduction in headache
frequent awakenings and some parasomnias. symptoms were obtained in 48% of the cases.
„ De Benedittis et al. Journal of Neurosurgical Sciences. 29:239 48, 1985.
„ De Giorgis et al. Drugs Under Experimental & Clinical
g g p
Research. 13(7):425 33, 1987.
20

21. Tension Headache Preventatives with some evidence
• Double blind RCT „ Magnesium: Chelated magnesium, magnesium oxide, and
• 78 patients with chronic T T HA
p slow release magnesium are likely to be the best
• L 5 hydroxytryptophan (5 HTP) 300 mg per day (n = 43) absorbed. The daily dose is 400 mg. Diarrhea may be a
or placebo (n = 35) for 8 weeks, after a washout period of limiting adverse effect in some patients.
2 weeksk „ Particularly useful in pregnancy.
• Follow up period of a further 2 weeks. „ Petasites hybridus (Petadolex): 75 mg twice daily for 1
• No significant decrease in HA days or HA intensity in the month, then 50 mg twice d l
h h daily.
group treated with 5 HTTP during TX
• Significant decrease in analgesics taken „ Feverfew: 100 mg daily.
• Significant decrease in the number of days with headache „ CoQ10: 300 mg daily.
during F/U „ Riboflavin (vitamin B2): 400 mg daily.
„ Alpha lipoic acid: 600 mg daily.
Ribeiro, CA. Headache 40(6):451-6, 2000
40(6):451-
Parker et al. Migraine and acupuncture
• Aust NZ J Med (1978) 8:589 593 & (1980) 10:192 198 „ 114 migraneurs 12 weeks of acupuncture (8 15 Tx) or
• Patients Common (61%) or classical migraine (
( ) g (39%) with mean of 19
) metoprolol (100 200 mg daily)
years duration. „ Outcome: # of migraine days in weeks 9 to 12
• 85 patients randomized to group 1 (chiropractic, n=30), group 2 „ Migraine days decreased by 2.5 +/ 2.9 days (baseline 5.8
(manipulation b medical d t n=27) or group 3 ( bili ti b
( i l ti by di l doctor, 27) (mobilization by +/ 2 5 d ) with acupuncture compared to 2 2 +/ 2 7
/ 2.5 days) ith t d t 2.2 / 2.7
physical therapist, n=28). days (baseline 5.8 +/ 2.9 days) in metoprolol group (P=
• Maximum of 2 months of twice weekly treatment. .721)
• Results At 2 months post treatment, group 1 had 40% fewer HA's and „ The proportion with reduction of migraine attacks by > or
43% less pain with HA's. In group 3, similar figures were 34% and 15%. =50%) was 61% for acupuncture and 49% for metoprolol
p
Mean pain intensity was 2.8 ( (VAS) in group 1 and 4.4 and 4.5 in groups
) d d
2 and 3 (p<0.01). „ Fewer adverse effects in the acupuncture
„ High drop out in the metoprolol group
Streng, et al. Headache. 46(10):1492-502, 2006
21

22. Migraine and acupuncture Migraine and acupuncture
• RCT: 28 migraineurs; real or sham acupuncture „ 302 migaineurs: Acupuncture, sham acupuncture, or
• Semi standardized and standardized minimal waiting list control
acupuncture were used „ 12 sessions per patient over 8 weeks.
– 16 Tx in 12 weeks. „ Compare 4 weeks before to 12 weeks and 21 to 24 weeks
• Similar reductions in: days with migraine, frequency of after randomization
migraine attacks, average duration of a migraine attack, „ HA days decreased by 2.2 (baseline 5.2) days with Tx; decrease
rate of rescue medication used, average headache
used by 2.2 (baseline 5 0) days in sham; and by 0.8 days (baseline
22 5.0) 08
severity 5.4) in waiting list group
– Nausea and vomiting not different.
g „ No difference between acupuncture and sham
• Showed that semi standardized acupuncture shows no „ Proportion of responders (> 50% less HA days):51% in Tx; 53%
difference from sham acupuncture in sham; 15% in waiting list
Alecrim-Andrade, et al.Cephalalgia. 26(5):520-9, 2006 Linde, et al. JAMA. 293(17):2118-25, 2005
Acupuncture in Migraine Acupuncture in T T Headache
p
• 140 migraine patients
• Acupuncture, minimal acupuncture (sham) or no
• Acupuncture group treated: verum acupuncture (3/wk) acupuncture with T T HA
ith
plus daily placebo
• 270 patients with episodic or chronic T T HA
• Control group: sham acupuncture plus flunarizine
flunarizine. • 12 sessions per patient over eight weeks.
i ti t i ht k
• Results: acupuncture group had better responder rates – Outcome: four weeks before with weeks 9 12
(>50% improvement) and fewer migraine days compared • HA days: decreased by 7 2 (SD 6 5) with TX; 6 6 (SD 6 0)
7.2 6.5) 6.6 6.0)
with the control group (P<.05) at 4 and 16 wks. with sham; and 1.5 (SD 3.7) with “waiting list”.
• No significant differences in VAS scores and SF 36
36. – Responders (> 50% reduction in HA days): 46% in Tx; 35%
p ( y) ;
sham, and 4% waiting
• No benefit over sham
Wang LP et al. Efficacy of acupuncture for migraine prophylaxis: a single-
blinded, double-dummy, randomized controlled trial . Pain, 06/01/2011
Melchart, et al. BMJ. 331(7513):376-82, 2005
331(7513):376-
22

23. Acupuncture in T T HA Acupuncture in chronic daily headache
p y
„ Acupuncture, relaxation training and physical
• RCT: 74 patients with CDH
training chronic tension type headache (CTTH) The
(CTTH).
• Compared medical management provided by neurologists
study comprised to medical management plus 10 acupuncture treatments.
„ 90 consecutive patients with CTTH
ti ti t ith • Medical management group: no improvement
d l
„ Measurements 4 weeks before, immediately after, and 3 and 6 • Medical management plus acupuncture:
months after the treatment period.
period – 3 0 points better (95% CI, 1.0 to 4.9) on the H d h I
3.0 i b CI 1 0 4 9) h Headache Impact
„ Immediately after the last treatment, the number of Test
– Increase >8 points on “role limitations” of SF36
p
headache free periods and of headache free days
– 3.7 times more likely to report less suffering at 6 weeks
was higher in the relaxation group compared with
the acupuncture group
Soderberg, et al. Cephalalgia. 26(11):1320-9, 2006
26(11):1320- Coeytaux, et al. Headache. 45(9):1113-23, 2005
Headache. 45(9):1113-
Migraine Migraine
„Criteria for late life migraine equivalents:
• Migraine is different in older individuals
„Fortification spectra/visual hallucination
and in children
„Slow evolution of visual or sensory symptoms.
– Older people have less severe headaches though
„Serial progression with delays between symptoms
can have many of the other things that go with
migraine “migraine equivalents”
g g q „Two or more identical attacks
– Children have shorter attacks and more vomiting „Duration greater than 20 minutes
(often cyclic vomiting) „Midlife flurry of attacks.
Midlife
„Complete recovery with normal exam
23

24. HA in children
Childhood Migraine
g
• By age 3, headache occurs in 3% to 8% of children.
• At age 5, 19.5% have headache, and by age 7, 37 to 51.5%
„Childhood migraine: have headaches.
„male preponderance, shorter attacks, • In 7 to 15 year olds, headache prevalence ranges from 57%
to 82%.
t 82%
prominent vomiting, abdominal pain/
• The prevalence increases from ages 3 to 11 in both boys
cyclic vomiting/ vertigo common, sleep and girls with higher headache prevalence in 3 to 5 year
disturbance common, minor head old boys than in 3 to 5 year old girls.
trauma may trigger good prognosis
trigger, prognosis. • Thus, the overall prevalence of headache increases from
preschool age children to mid adolescence when examined
using various cross sectional studies.
– Bigal M.E., Liberman J.N., Lipton R.B., et al: Age dependent prevalence and
clinical features of migraine. Neurology 67. (2): 246 251, 2006
Riboflavin for HA in children Beware the diagnosis of Cluster HA
„ Retrospective study reports on our experience of using – it is often wrong!
riboflavin for migraine prophylaxis in 41 pediatric and
„ Diagnosis:
adolescent patients, who received 200 or 400 mg/day single
„ Demographics: Male 6:1, Older onset (peak 20 50)
oral dose of riboflavin for 3, 4 or 6 months.
„ Periodicity: "headaches with a clock , especially at night
headaches clock"
„ 77.1% reported that abortive drugs were effective for
„ Character:
controlling ictal events.
„ paroxysmal/explosive/unilateral/periorbital pain, ipsilateral nasal
„ During the follow up, 68.4% of cases had a 50% or greater congestion/ lacrimation/ sweating/ Horner's syndrome/ conjunctival
reduction in frequency of attacks and 21.0% in intensity. injection.
„ Riboflavin well tolerated. „ Location: 80 85% h
have ocular pain, 80 85% h
l have temporal pain,
l
„ Condò M, Posar A, Arbizzani A, Parmeggiani A. Riboflavin prophylaxis in pediatric 80 85% have frontal pain, 50% have maxillary pain, 50% have
and adolescent migraine J Headache Pain. 2009 Oct;10(5):361 5
migraine. Pain 5. zygomatic pain 20 25% have nasal pain 20 25% have parietal
pain, pain,
pain, 20 25% have occipital pain
24

25. Cluster Cluster
„ Treatment:
„P h d h O
Per headache: Oxygen especially f nocturnal
i ll for l
attacks. Ergotamine. Lidocaine intranasal infusion.
Capsaicin.
Capsaicin DHE
„ Prophylaxis: treatment for projected duration of
cluster. Ergotamine, Prednisone Methysergide
cluster Ergotamine Prednisone, Methysergide,
Lithium, Indocin, calcium channel blockers
„ ?Occipital nerve block, Surgery
block
„ Manipulation?
Cervicogenic Headache
g Cervicogenic Headache
• Neck motion, particularly rotation and flexion/extension
„ Cervicogenic headache appears to be a relatively
is limited in cervicogenic headache
common form of headache, similar to migraine in
headache
– 51 control subjects and 90 HA patients (28 migraine, 34 T T, and
prevalence. 28 cervicogenic)
„ F t fi patients with h d h 5 or more days a month
Forty five ti t ith headaches d th
– Significant differences between cervicogenic headache and the
were interviewed and examined with respect to the IHS
other groups for rotation & flexion/extension, but not lateral
criteria for cervicogenic headache.
g
neck movement
k t
„ Of the 45 persons examined, eight fulfilled the diagnostic
– “Reduced neck mobility is one of the major criteria for this
criteria for cervicogenic headache, equivalent to a
diagnosis,
diagnosis it emphasizes the need for systematic, objective neck
systematic
prevalence in the headache group of 17.8% .
mobility measurements in the individual patient to substantiate
„ Nilsson. Spine. 20:1884 8, 1995.
the diagnosis.”
• Zwart JA. Headache. 37:6 11, 1997.
25

26. Cervicogenic headache Conclusions
„ Chiropractic treatment has significant benefit on • More than 21 million Americans suffer from
patients with cervicogenic HA migraine and other severe headaches
„ 53 patients with cervicogenic headache randomized to
chiropractic Tx twice per week for 3 weeks or low level laser • Most had seen a physician but many (up to half)
treatment of the upper neck and deep friction massage of undiagnosed
lower neck and upper back.
„ Analgesic use dropped 36% headache hours per day dropped
36%, • 85% had cancelled or delayed social activities;
% y ;
69% and headache intensity dropped 36% in the manipulated 80% of employees have their work effected.
group (as compared with no decrease, 36% decrease and 17%
decrease in the control group respectively).
group, respectively) • Effective migraine treatment improves patients
„ Nilsson et al. JMPT. 20(5):326 30, 1997 lives.
Conclusions
• Many patients don’t know they have migraine or
migranous HA
Managing Headache
g g
• Only 1/3 of very satisfied w/ treatment
• Most patients had tried almost 5 options before
Rand Swenson, D.C., M.D., Ph.D.
effective treatment found
Professor of Neurology and Anatomy
• Migraine is an expensive condition in terms of both
health care and societal costs Dartmouth Medical School
Hanover, NH
• A natural approach can make a significant difference
in patients lives
26