NEUROLOGY/HEADACHE
| PEDIATRIC NEUROLOGY: CASE VIGNETTES —Kenneth J. Mack, MD, PhD, Associate Professor of Neurology,
Mayo Clinic, Rochester, Minnesota
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Migraine
| Case 1: 12-yr-old boy presents with weekly headaches; pain bifrontal and throbbing; patient avoids bright lights; nauseated
during headache; lasts ≈60 min; more frequent during school year, almost nonexistent during summer
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| Diagnosis: typically made by history; if patient consults physician about headache, diagnosis likely migraine; pain—
severe; frontal (in back of head in one third of patients); questions—do lights hurt your eyes (or other strong sensory
stimuli)? are you nauseated by headaches? does sleep relieve headaches? if yes to all 3 or to 2 of 3 questions, problem
most likely migraine; many call it sinus or allergy headache
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| Evaluation: magnetic resonance imaging (MRI) important if atypical features present (eg, weakness, seizures, papilledema);
American Academy of Neurology (AAN) meta-analysis—adults with chronic headaches (>6 mo); of 797 patients,
only 3 had MRI or computed tomography (CT) that required intervention; 2 had seizures or history of seizures; 2
had focal neurologic deficits; if neurologic examination and development normal, and no history of seizures, unlikely
that imaging beneficial; MRI can cause unnecessary anxiety; laboratory studies—thyroid hormone, complete blood
count (CBC); low thyroid hormone levels more important in adults than children; electroencephalography (EEG)—not
useful
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 | Avoid triggers: in adults, most common triggers stress and lack of sleep; average teenager needs 9.0 to 9.5 hr of sleep
nightly; busy schedule frequently source of stress; missing breakfast; weather (eg, storm front); foods (monosodium
glutamate [MSG]; nitrates, eg, in wine); hormonal changes associated with menstrual cycle; motion (eg, car or amusement
park rides); bumps to head, eg, during sports
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| Pain control: pain begets pain (treat early); nonsteroidal anti-inflammatory drugs (ibuprofen great in short-acting headaches;
naproxen [Naprosyn] for longer headaches); triptans (eg, sumatriptan [Imitrex]) beneficial; many over-the-
counter (OTC) migraine medications contain caffeine (with frequent use, caffeine can cause rebound)
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| Prevention: if >2 headaches per week, consider daily medication; drugs include amitriptyline, β-blockers, and anticonvulsants
(each effective in ≈50% of patients); riboflavin works well in ≈50% of patients (pediatric dose 100 or 200 mg/
day)
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Chronic Daily Headache
| Case 2: 16-yr-old presents with 5-yr history of migraines; daily headache since last September; rates pain 11 out of 10;
takes 2 hr to fall asleep; patient feels sad and frustrated since headaches started
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| Diagnosis and evaluation: chronic daily headache defined as >15 headache days monthly for >3 mo; typically occur
in patients with personal history of migraine (probable migraine variant); occurs in ≈4% of young women (2% of men);
MRI may be helpful to reassure patients; thyroid hormone levels, CBC, erythrocyte sedimentation rate (ESR), and Lyme
titers reasonable; many patients have low riboflavin levels
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| Types of headache: 1) daily headaches (some labeled tension-type headaches); avoid pain relievers; 2) severe intermittent
headache
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| Prognosis: usually improved with better sleep; “cured” patients become episodic migraineurs
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Epilepsy
| Case 3: 8-yr-old child had generalized tonic-clonic seizure at school; development normal; no past history of seizures,
head trauma, or infection; on examination 2 yr after seizure, child normal
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| Diagnosis: made by history; epilepsy defined as ≥2 seizures for no apparent reason (as opposed to first-time seizure);
EEG—diagnostic study of choice; may predict types of seizures patient may be prone to in future (does not inform physician
about past events); 50% of epileptics have normal first EEG; 10% of normal patients have abnormal EEG; attention-deficit
disorder (ADD) population have frequency of epileptiform abnormalities (in some studies, 6% have
abnormalities, but only 1% have clinical seizures)
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| Evaluation: EEG—helpful in defining seizure type; blood studies—probably helpful in inpatient on IV fluids (not in
typical outpatient); MRI (AAN recommendations)—optional after single episode; consider it if seizure focal, papilledema
present, or child has recurrent episodes
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| Treatment: antiepilepsy medications decrease probability of another seizure, but not curative; anticonvulsants used only after
second seizure (only ≈40% of patients have second event); partial complex seizures—levetiracetam (Keppra); carbamazepine
(Tegretol); oxcarbazepine (Trileptal); primary generalized epilepsy—valproic acid (Depakote); lamotrigine
(Lamictal); if seizures not under control within 3 mo, refer to neurologist
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| Prognosis: after first generalized seizure, only 40% have second episode; if seizures recurrent, use medications for 1 to 2
seizure-free years
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Tics
| Case 4: 7-yr-old boy presents with 1-yr history of facial grimacing, eye blinking, and throat clearing; recently started on
methylphenidate (Ritalin) for attention-deficit/hyperactivity disorder (ADHD); eye blinking worse since then
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| Diagnosis: Tourette syndrome—vocal and motor tics >1 yr; transient tic disorder—duration <1 yr; chronic tic
disorder—motor or vocal tics >1 yr
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| Evaluation: MRI and EEG almost always normal; ceruloplasmin level to rule out Wilson’s disease; thyroid levels routine,
but hyper- or hypothyroidism does not typically present with tics; CBC to rule out neuroacanthocytosis (rare); comorbid
symptoms—ADHD; obsessive-compulsive disorder (OCD); sadness; anxiety; avoid antistreptolysin-O (ASO)
antibodies whenever possible; pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection
(PANDAS); Sydenham’s chorea associated with streptococcal infection (patients improve after 2 mo; tics persist for
years); problem of diagnosis—incidence of streptococcal infection high in children (20% have positive cultures); high
ASO titers and positive throat cultures common in children without active disease; tics occur in 1% of population; no effective
treatment—daily antibiotic prophylaxis does not seem to work; plasmapheresis not recommended or effective in
everyone
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| Treatment: do not treat before preteen years, if possible; clonidine (Catapres) or guanfacine (Tenex)—first-line drugs;
side effect tiredness; treatment effective ≈1 yr; neuroleptics—eg, risperidone (Risperdal) or olanzapine (Zyprexa) most
effective, but side effects worrisome; tardive dyskinesia occurs in <1% of children; weight gain; bedwetting; attentional
problems occur in 70% of patients; stimulants not contraindicated, but worsen tics in some patients; atomoxetine (Strattera)
not as effective as stimulants for attention, but does not aggravate tics
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| Prognosis: 1% of third graders have tics; usually start between 3 and 7 yr of age (tend to worsen over time; peak at 10-12 yr
of age); in adolescence, some children stabilize; can worsen with head injuries, anxiety, or frequent infections; in early adult
years, one third resolve (one third improve; one third persist)
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Delayed Development
| Case 5: 12-mo-old child; parents concerned about developmental progress; uneventful pregnancy, labor, and delivery; patient
started to sit at 12 mo of age; does not say any syllables or words; mild central hypotonia
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| Diagnosis: differential diagnosis broad; empathize with parents; be honest (parents dislike euphemisms and lack of information;
if child mentally retarded, parents want to know early); referral—indicated for patients with multiple organ-system
involvement; neurologist helpful; for patients with autistic tendencies or for school issues, developmental pediatrics
useful
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| Evaluation: MRI of head one of most informative studies; routine chromosome studies helpful in children with intelligence
quotient (IQ) <50; in those with IQ of 50 to 70, fragile X or telomere probes helpful; in patients with IQ <50, specific
etiology found ≈50% of time (with IQ 50-70, ≈10%); reversible causes—urine organic acids; biotinidase levels;
Smith-Lemli-Opitz screen for treatable neurologic conditions
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| Treatment: goal early diagnosis and intervention; treatable target symptoms—seizures; ADHD; sleep disturbance
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| COMPLEMENTARY AND ALTERNATIVE APPROACHES TO HEADACHE —Paul Graham Fisher, MD, Associate
Professor, Neurology, Pediatrics, Neurosurgery, and Human Biology, Stanford University School of Medicine, and The
Beirne Family Director of Neuro-Oncology at Packard Hospital, Stanford, California
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| Diagnostic approach: exclude ominous headache; think about migraine; consider nonpharmacologic approaches to
headache or chronic pain in addition to pharmacologic approaches
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| Reasons to consider nonpharmacologic treatment: poor tolerance of or response to pharmacologic treatment;
medical contraindication to pharmacologic treatment (eg, pregnancy); patient preference
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| Vitamins: hydroxocobalamin (B12 ) not well absorbed via gastrointestinal (GI) route; pyridoxine (B6 ) sometimes useful in
pyridoxine-dependent seizures (superdosing can cause neuropathy); riboflavin (B2 )—may work as prophylaxis against
migraine (in speaker’s experience, good efficacy in 50% of patients); dose 400 mg/day (recommended daily allowance
[RDA] 2 mg); no reported toxicity; in study by Schoenen, nearly 60% of patients had >50% reduction in headaches (may
require few months before effect); studies of triptans—placebo response rate 35% to 40%
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| Magnesium: long history of medicinal use; may have effect as calcium channel blocker; may promote vasoconstriction;
may have secondary effects on platelet aggregation and substance P; migraine prevention—in adult data, dosed once or
twice daily (RDA for children ≈50% that for adults); seeming role in prevention; side effect laxative effect; abortive
therapy—much less data; less effective than metoclopramide (Reglan) or prochlorperazine
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| Coenzyme Q10: mitochondrial defect possible etiology of migraine; optimizes mitochondrial function and oxidative
phosphorylation; not clear whether migraine etiology neurochemical, vascular, or ischemic; study by Rozen—150 mg/
day as prophylaxis; majority of patients had >50% reduction in headaches
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| Feverfew (Tanacetum parthenium): long history as medicinal; “medieval aspirin”; inhibits serotonin release; may inhibit
prostaglandins and histamines; dose 2 to 3 leaves or 25 to 100 mg/day; herbals not well controlled by Food and
Drug Administration (concentration highly variable); migraine prevention (study by Murphy)—dose 50 to 100 mg;
regimen 4 mo on 4 mo off; 24% fewer headaches; less nausea and vomiting; some dramatic responders; difficult to sort
out placebo response; safety—if discontinued abruptly, some patients develop severe withdrawal headache; mild GI upset;
stimulation of uterine contractions (can cause termination of pregnancy in adolescent); OTC products—MigreLief
(riboflavin, magnesium, and feverfew); Migra-Profen (feverfew, kava kava, Valerian root, and Jamaican dogwood bark)
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| Butterbur (Petadolex): anti-inflammatory effect (may inhibit leukotriene synthesis); calcium channel effect not clear;
used as prophylaxis; dosing 50 to 100 mg, used twice daily; study by Lipton—improved pain control using 75 mg bid (significantly
better than placebo); 50 mg not significantly better than placebo
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| Physical treatments (overview): acupuncture; Botulinum toxin type A (Botox); massage; chiropractic (head thrusts
“off limits”; risk for carotid dissection or vertebral bone displacement); yoga or Qigong (not much data)
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| Acupuncture and National Institutes of Health (NIH): effective in adults—for postoperative pain, chemotherapy-related
nausea and vomiting, and postoperative dental pain; headaches—typical treatment 4 to 8 sessions; 20 to 30
min for several months as prophylaxis; studies—30% to 50% demonstrate improvement in headaches; migraine prevention
(sham-controlled studies)—head-to-head sham and acupuncture results similar; both more effective than control
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| Botulinum toxin type A: applied to temporalis, frontalis, or along sternocleidomastoid or latissimus dorsi; study by
Miller—30 patients; with several treatments, some improvement; in adult data, 70% reported improvement; decreased
frequency of attacks; study by Blumenthal—several treatments over several months; improvement in migraines, chronic
daily headaches, tension-type headaches, and mixed headaches; need better data and testing
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| Progressive muscle relaxation: altering baseline reception and threshold for pain; affects how body interprets and responds
to pain; seems helpful; part of practice of some occupational therapists; good results; requires few sessions, and families
often very willing to try; evidence—some improvement in migraine and pediatric pain and tension-type headache
(small numbers)
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| Biofeedback: useful; takes advantage of electromechanical or electrical feedback from normal physiologic processes
(eg, respiratory rate or reception of pain); moves locus of control away from parent to child; in recent study, 1 or 2 sessions
associated with reduction of headaches up to 2 yr later; supervised by psychologist, physical therapist, or occupational
therapist; evidence—migraine; pediatric migraine; tension-type headaches; clearly works
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| Hypnosis: less data for managing headache (more data in controlling chronic vomiting and abdominal pain); getting child
to focus attention on positive targets
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| Cognitive behavioral therapy (CBT): theory that if patient more positive and does not dwell on pain, pain decreases
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| Efficacy (study by Holroyd): relaxation, biofeedback, and CBT all work to some degree
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| Prevention of migraine: no practice guidelines or evidence statements for children; practice parameter for adults
(AAN)—relaxation therapy; biofeedback; cognitive behavioral therapy
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Educational Objectives
| The goal of this program is to educate the listener about pediatric neurology and headache. After hearing and assimilating
this program, the clinician will be better able to:
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| 1. Choose appropriate medical therapy for managing pediatric migraine.
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| 2. Manage patients after a first-time generalized seizure.
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| 3. Choose appropriate medical therapy for managing tics.
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| 4. Describe alternative nutritional therapies for headache.
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| 5. Describe alternative physical therapies for headache.
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Discussed on This Program
Amitriptyline HCl [Elavil]
Atomoxetine HCl [Strattera]
Botulinum toxin type A [Botox, Botox Cosmetic]
Butterbur (Petasites vulgaris, Petasites hybridus)
Capsaicin (several formulations and trade names)
Carbamazepine [Carbatrol, Epitol, Tegretol, Tegretol-XR]
Clonidine HCl [Catapres, Duraclon]
Ginkgo (Ginkgo biloba)
Guanfacine HCl [Tenex]
Hydroxocobalamin, crystalline (vitamin B12 ) [Hydro Cobex, Hydro-Crysti-12, LA-12]
Ibuprofen (several formulations and trade names)
Lamotrigine [Lamictal, Lamictal Chewable Dispersible]
Levetiracetam [Keppra]
Magnesium (several formulations and trade names)
Methylphenidate HCl [Concerta, Metadate CD, Metadate ER, Methylin, Methylin ER, Ritalin, Ritalin LA, Ritalin–SR]
Metoclopramide [Clopra, Maxolon, Metoclopramide Intensol, Octamide, Octamide PFS, Reclamide, Reglan]
Naproxen [Aleve, Anaprox, Anaprox DS, EC-Naprosyn, Naprosyn, Naprelan]
Olanzapine [Zyprexa, Zyprexa Intramuscular, Zyprexa Zydis]
Oxcarbazepine (oxycarbamazepine) [Trileptal]
Prochlorperazine [Compazine, Compro]
Pyridoxine HCl (B6 ) [Aminoxin, Vitelle Nestrex]
Riboflavin (B2 )
Risperidone [Risperdal, Risperdal Consta, Risperdal M-TAB]
Sumatriptan succinate [Imitrex]
Valproic acid [Depacon, Depakene, Depakote, Depakote ER]
Resources
American Academy of Neurology: www.aan.com
Suggested Reading
Damen L et al: Symptomatic treatment of migraine in children.Pediatrics 116:e295, 2005; Gladstein J, Mack KJ:
Chronic daily headache in adolescents. Pediatr Ann 34:472, 2005; Hershey AD: Pediatric headache. Pediatr Ann
34:426, 2005; Kabbouche MA, Linder SL: Acute treatment of pediatric headache in the emergency department. Pediatr
Ann 34:466, 2005; Kroener-Herwig B, Denecke H: Cognitive-behavioral therapy of pediatric headache: are
there differences in efficacy between a therapist-administered group training and a self-help format? J Psychosom Res
53:1107, 2002; Lewis D et al: Practice parameter: pharmacological treatment of migraine headaches in children and adolescents:
report of the American Academy of Neurology Quality Standards Subcommittee and the Practice Committee of
the Child Neurology Society. Neurology 63:2215, 2004; Lewis DW et al: Prophylactic treatment of pediatric migraine.
Headache 44:230, 2004; Lewis DW et al: The treatment of pediatric migraine. Pediatr Ann 34:448, 2005; Mack KJ:
What incites new daily persistent headache in children? Pediatr Neurol 31:122, 2004; Major PW et al: Triptans for
treatment of acute pediatric migraine: a systematic literature review. Pediatr Neurol 29:425, 2003; Millichap JG, Yee
MM: The diet factor in pediatric and adolescent migraine. Pediatr Neurol 28:9, 2003; Pothmannn R, Danesch U:
Migraine prevention in children and adolescents: results of an open study with a special butterbur root extract. Headache
45:196, 2005;Powers SW, Andrasik F: Biobehavioral treatment, disability, and psychological effects of pediatric
headache. Pediatr Ann 34:461, 2005; Rosenblum RK, Fisher PG: A guide to children with acute and chronic headaches.
J Pediatr Health Care 15:229, 2001;
Faculty Disclosure
In adherence to ACCME guidelines, the Audio-Digest Foundation requests all lecturers to disclose any significant financial relationship
with the manufacturer or provider of any commercial product or service discussed. For this issue, the faculty reported
nothing to disclose.
Dr. Mack was recorded at Pediatric Days, presented September 8-9, 2005, in Chicago by Mayo Clinic College of Medicine,
Rochester, Minnesota; Dr. Fisher was recorded at Clinical Pediatrics, presented February 16-19, 2006, in Palm
Springs, California, by the American Academy of Pediatrics, California, Chapter 2. The Audio-Digest Foundation thanks
Drs. Mack and Fisher and the sponsors for their cooperation in the production of this program.
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