Migraine - Nelson Review

Migraine

The prevalence of migraine among school-aged children between 7 and 15 yr of age was 4% in a comprehensive Swedish study and ranges from 8 to 23% in adolescents.

Cortical spreading depression (CSD), a phenomenon thought to be responsible for the aura of migraine, is associated with elevation of CNS hydrogen and potassium ions, with the release of glutamate and nitrous oxide. These changes result in regional cortical oligemia and activation of the caudal portion of the trigeminal ganglion. Excitation of the trigeminal-vascular system initiates the release of vasoactive intestinal polypeptides causing vasodilation followed by extravasation of plasma proteins from the dural vessels resulting in localized inflammation of the dural vessels. Neurogenic vascular inflammation causes excitation of pain sensitive receptors and the onset of pain. CSD is considered to be an inherited physiologic response to a variety of stimuli that are responsible for triggering the migraine process.

Migraine without aura

This migraine is not associated with an aura and is the most prevalent type of migraine in children. The headache is throbbing or pounding and tends to be unilateral at onset or throughout its duration but may also be located in the bifrontal or temporal regions. It may not be hemicranial in children and is less intense compared with the migraine in adults. The headache usually persists for 1–3 hr, although the pain may last for as long as 72 hr. The pain may inhibit daily activity, because physical activity aggravates the pain. A characteristic feature of childhood migraine is intense nausea and vomiting, which may be more bothersome than the headache. The vomiting may be associated with abdominal pain and fever; conditions such as appendicitis and a systemic infection may be erroneously confused with the primary diagnosis. Additional symptoms include extreme paleness, photophobia, light-headedness, phonophobia, osmophobia (aversion to odors), and paresthesias of the hands and feet. A positive family history, particularly on the maternal side, is present in ≈90% of children with migraine without aura. Considerable caution should be exercised when making the diagnosis of migraine in the absence of a positive family history. Additional features of all migraines may include near synchrony with perimenstrual or periovulation timing, gradual appearance after sustained exercise, relief with sleep, stereotypical prodromes (hypersomnia, food craving, irritability, moodiness), precipitation by food or odors, and onset after a letdown or high period of stress

Migraine with an Aura.

In this disorder, an aura precedes the onset of the headache. Visual auras are uncommonly described by young children with migraine, but when they occur they may take the form of blurred vision, scotoma (an area of depressed vision within the visual field), photopsia (flashes of light), fortification spectra (brilliant white zigzag lines), or irregular distortion of objects. Some patients also have vertigo and light-headedness during this stage of the headache. Sensory symptoms include perioral paresthesias and numbness of the hands and feet. Distortions of body image (Alice in Wonderland syndrome) may predominate as a prelude to a classic migraine headache. After the onset of the aura, the patient develops typical symptoms of a migraine as described earlier.

Hemiplegic migraine is considered a migraine aura and is characterized by the onset of unilateral sensory or motor signs during an episode of migraine. Hemisyndromes are more common in children than in adults and may be characterized by numbness of the face, arm, and leg; unilateral weakness; and aphasia. Hemiplegic migraine in an older child or adolescent has a relatively good prognosis, and a positive family history of similar hemiplegic events is often elicited. Familial hemiplegic migraine (FHM) is an autosomal dominant disorder. FHM is characterized by hemiplegia during the headache and, in some kindreds, progressive cerebellar atrophy.

Basilar-type migraine is considered to represent a precursor of childhood migraine. Brainstem signs predominate in these patients because of vasoconstriction of the basilar and posterior cerebral arteries. The major symptoms include vertigo, tinnitus, diplopia, blurred vision, scotoma, ataxia, and an occipital headache. The pupils may be dilated, and ptosis may be evident. Alterations in consciousness followed by a generalized seizure may result. After the attack, there is a complete resolution of the neurologic symptoms and signs. Most affected children have a strongly positive family history of migraine

TABLE 595-3 -- Diagnostic Criteria for Migraine

WITHOUT AURA

A At least five attacks B Headache attack lasts 4–72 hr (untreated or unsuccessfully treated). C Headache has at least two of the following characteristics: Unilateral location Pulsating quality Moderate or severe intensity Aggravation by or avoidance of routine physical activity (i.e., walking or climbing stairs) D During headache at least one of the following: Nausea, vomiting, or both Photophobia and phonophobia E Not attributed to another disorder

WITH AURA (CLASSIC MIGRAINE)

A At least two attacks B Migraine aura fulfills criteria for typical aura, hemiplegic aura, or basilar-type aura. C Not attributed to another disorder

TYPICAL AURA

1 Fully reversible visual, sensory, or speech symptoms (or any combination) but no motor weakness 2 Homonymous or bilateral visual symptoms including positive features (e.g., flickering lights, spots, lines) or negative features (e.g., loss of vision), or unilateral sensory symptoms including positive features (e.g., visual loss, pins and needles) or negative features (i.e., numbness), or any combination 3 At least one of: a) At least one symptom develops gradually over a minimum of 5 min, or different symptoms occur in succession, or both b) Each symptom lasts for at least 5 min and for no longer than 60 min 4 Headache that meets criteria for migraine without aura begins during the aura or follows aura within 60 min

From Silberstein SD: Migraine. Lancet 2004;363:381–391.

The most common precipitators of migraine headaches are stress, fatigue, and anxiety. The parents may be asked to create a diary or calendar relating the onset of headache to a particular food to determine if dietary factors are responsible for the child's migraine. Elimination of the incriminating foodstuff is indicated if the history suggests a relationship between the ingestion of a particular food and the onset of headache

TABLE 595-2 -- Indications for Neuroimaging in a Child with Headaches

Abnormal neurologic signs Recent school failure, behavioral change, fall-off in linear growth rate Headache awakens child during sleep; early morning headache, with increase in frequency and severity Periodic headaches and seizures coincide, especially if seizure has a focal onset Migraine and seizure occur in the same episode, and vascular symptoms precede the seizure (20–50% risk of tumor or arteriovenous malformation) Cluster headaches in child; any child <5–6> Focal neurologic symptoms or signs developing during a headache (i.e., complicated migraine) Focal neurologic symptoms or signs (except classic visual symptoms of migraine) develop during the aura, with fixed laterality; focal signs of the aura persisting or recurring in the headache phase Visual graying-out occurring at the peak of a headache instead of the aura Brief cough headache in a child or adolescent

Modified from Barlow CF: Headaches and Migraine in Childhood. Philadelphia, JB Lippincott, 1984, p 205.

Intravenous prochlorperazine, 0.15 mg/kg (max 10 mg), is highly effective in aborting intractable migraine in children who have not responded to acute management of the headache

Management of an acute attack of migraine should include the use of analgesics and antiemetics ( Table 595-4 ). Most migraine headaches in children can be treated by the judicious use of acetaminophen (15 mg/kg) or ibuprofen (7.5–10 mg/kg) dispensed in the gel capsule formulation, particularly if the headaches are mild, infrequent, and of short duration. The child usually prefers to rest in a quiet, darkened room and typically awakens, refreshed and headache free, several hours later after a deep sleep. Triptans (e.g., Sumatriptan) are specific and selective 5-hydroxytryptamine receptor agonists that are effective abortive drugs in treating the acute phase of migraine with and without aura if the use of conventional analgesics is ineffective. Sumatriptan may be administered subcutaneously, nasally, or orally. The nasal spray formulation is the preferred route of administration for children. The suggested dose is 5 mg in children <25 style="background: yellow none repeat scroll 0% 0%; -moz-background-clip: border; -moz-background-origin: padding; -moz-background-inline-policy: continuous;">10 mg (two sprays) in those weighing 25–50 kg, and 20 mg sumatriptan in children ≥50 kg

ADHD - Atention deficiency and hiperactivity disorder

ADHD

Epidemiology

The Centers for Disease Control and Prevention

(2005) conducted the National Survey of Children’s

Health during January 2003Y2004, asking parents of

more than 100,000 children ages 4 to 17 years whether

their child had ever been diagnosed with ADHD or

received medication treatment (as opposed to currently

being treated). The rate of lifetime childhood diagnosis

of ADHD was 7.8%, whereas 4.3% (or only 55% of

those with ADHD) had ever been treated with

medication for the disorder

Although only

40% of 18- to 20-year-old Bgrown up^ ADHD

patients met the full criteria for ADHD

Comorbidities

Studies have shown that 54%Y84% of

children and adolescents with ADHD may meet criteria

for oppositional defiant disorder (ODD); a significant

portion of these patients will develop conduct disorder

Etiology

Specifically, a meta-analysis of

83 studies with more than 6,000 subjects showed that

patients with ADHD have impairments in the executive

functioning domains of response inhibition, vigilance,

working memory, and some measures of planning.

Faraone et al. (2005b) reviewed 20 independent

twin studies that estimated the heritability (the

amount of phenotypic variance of symptoms attributed

to genetic factors) to be 76%.

Faraone et al. (2005b) identified eight genes in which

the same variant was studied in three or more studies;

seven of which showed statistically significant evidence

of association with ADHD (the dopamine 4 and 5

receptors, the dopamine transporter, the enzyme

dopamine "-hydroxylase, the serotonin transporter

gene, the serotonin 1B receptor, and the synaptosomalassociated

protein 25 gene).

Screening

The clinician should perform a detailed interview with

the parent about each of the 18 ADHDsymptoms listed in

DSM-IV. For each symptom, the clinician should

determine whether it is present as well as its duration,

severity, and frequency

Children suffering a severe head injury may develop

symptoms of ADHD, usually of the inattentive

subtype. Hyperthyroidism,

which can be associated with hyperactivity and

agitation, rarely presents with ADHD symptoms

alone but with other signs and symptoms of excessive

thyroid hormone levels.

Academic impairment is commonly due to the ADHD

itself. However, if there is no clear evidence of an

improvement in academic performance in 1 to 2 months

despite improvement of the ADHD, then psychological

testing for learning disorders is indicated

Treatment

It is also clear that behavior therapy alone

can produce improvement in ADHD symptoms

relative to baseline symptoms or to wait-list controls

Jadad et al. (1999)

reviewed 78 studies of the treatment of ADHD; six of

these studies compared pharmacological and nonpharmacological

interventions. The reviewers reported that

studies consistently supported the superiority of

stimulant over the nondrug treatment. Twenty studies

compared combination therapy with a stimulant or

with psychosocial intervention, but no evidence of an

additive benefit of combination therapy was found.

In the MTA study, children with ADHD were

randomized to four groups: algorithmic medication

treatment alone, psychosocial treatment alone, a

combination of algorithmic medication management

and psychosocial treatment, and community treatment.

Algorithmic medication treatment consisted of

monthly appointments in which the dose of medication

was carefully titrated according to parent and teacher

rating scales. Children in all four treatment groups

showed reduced symptoms of ADHD at 14 months

relative to baseline. The two groups that received

algorithmic medication management showed a superior

outcome with regard to ADHD symptoms compared

with those that received intensive behavioral treatment

alone or community treatment (MTA Cooperative

Group, 1999a [rct]).

Behavior therapy may be

recommended as an initial treatment if the patient’s

ADHD symptoms are mild with minimal impairment,

the diagnosis of ADHD is uncertain, parents reject

medication treatment, or there is marked disagreement

about the diagnosis between parents or between parents

and teachers.

Treatment

The physician is free to choose any of the two

stimulant types (MPH or amphetamine) because

evidence suggests the two are equally efficacious in

the treatment of ADHD.

Single daily dosing is associated with greater

compliance for all types of medication, and long-acting

MPH may improve driving performance in adolescents

relative to short-acting MPH (Cox et al., 2004 [rct]).

Physicians may use long-acting forms as initial

treatment; there is no need to titrate to the appropriate

dose on short-acting forms and then Btransfer^ children

to a long-acting form. Short-acting stimulants are often

used as initial treatment in small children (<16>

weight), for whom there are no long-acting forms in a

sufficiently low dose.

On average, there is

a linear relationship between dose and clinical response:

that is, in any group of ADHD subjects, more subjects

will be classified as responders and there is a greater

reduction in symptoms at the higher doses of stimulant.

There is no evidence of a global Btherapeutic^ window

in ADHD patients. Each patient, however, has a unique

dose-response curve.

After selecting the starting dose, the physician may

titrate upward every 1 to 3 weeks until the maximum

dose for the stimulant is reached, symptoms of ADHD

remit, or side effects prevent further titration, whichever

occurs first

Eight of the nine studies supported the efficacy of MPH

in the treatment of preschoolers with ADHD at

milligram-per-kilogram doses that were comparable

with those used in school-age children

Of note, only 37 of 279 enrolled

parents thought that the behavior training resulted in

significant or satisfactory improvement

Results from the short-term, open-label, run-in and

double-blind, crossover studies do show that MPH is

effective in preschoolers with ADHD (Greenhill et al.,

2006a). The mean optimal dose of MPH was found to

be 0.7 T 0.4 mg/kg/day, which is lower than the mean

of 1.0 mg/kg/day found to be optimal in the MTA

study with school-age children

Atomoxetine is a noradrenergic reuptake inhibitor

that is superior to placebo in the treatment of ADHD in

children, adolescents, and adults

Michelson et al. (2002) showed that although

atomoxetine was superior to placebo at week 1 of the

trial, the greatest effects were observed at week 6,

suggesting the patient should be maintained at the full

therapeutic dose for at least several weeks to obtain the

drug’s full effect. At the end of the treatment period,

atomoxetine led to a significant reduction in ratings of

symptoms of both ADHD and anxiety relative to

placebo, showing the drug to be efficacious in the

treatment of both conditions.

in a meta-analysis of atomoxetine and stimulant studies,

the effect size for atomoxetine was 0.62 compared with

0.91 and 0.95 for immediate-release and long-acting

stimulants, respectively

Bupropion is a noradrenergic antidepressant

that showed modest efficacy in the treatment of

ADHD in one double-blind, placebo-controlled trial

(Conners et al., 1996 [rct]). It is contraindicated in

patients with a current seizure disorder. It can be given in

either immediate-release or long-acting form, but may

not come in pill sizes small enough for children who

weigh <25>

A

gradual titration is required and clinical consensus

suggests the !-agonists are more successful in treating

hyperactive/impulsive symptoms than inattention

symptoms, In recent years clinical consensus has led to the use of clonidine as adjunctive therapy to treat tics

or stimulant-induced insomnia rather than as a primary

treatment for ADHD.

For stimulant medications, the most common side

effects are appetite decrease, weight loss, insomnia, or

headache. Less common side effects of stimulants

include tics and emotional lability/irritability.

If the patient’s ADHD

symptoms respond adequately only to a stimulant

medication that induces tics, then combined pharmacotherapy

of the stimulant and an !-agonist (clonidine

or guanfacine) is recommended (Tourette’s Syndrome)

Controlled trials of stimulants do not support the

widespread belief that stimulant medications induce

aggression. Indeed, overall aggressive acts and antisocial

behavior decline when ADHD patients are treated with

stimulants

In 12 controlled trials involving

1,357 patients taking atomoxetine and 851

taking placebo, the average risk of suicidal thinking

was 4/1,000 in the atomoxetine-treated group versus

none in those taking placebo.

examined all of the available

data and concluded that stimulant treatment may be

associated with a reduction in expected height gain, at

least in the first 1 to 3 years of treatment