Clinical EEG and Neuroscience

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Utility of the Electroencephalogram in Attention Deficit Hyperactivity Disorder

J. Gordon Millichap, John J. Millichap and Cynthia V. Stack
Clin EEG Neurosci 2011 42: 180
DOI: 10.1177/155005941104200307

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CLINICAL EEG and NEUROSCIENCE
Utility of the Electroencephalogram in
Attention Deficit Hyperactivity Disorder
J. Gordon Millichap, John J. Millichap and Cynthia V. Stack
Key Words
Attention Deficit Hyperactivity Disorder
Electroencephalogram
Pediatrics
ABSTRACT
An electroencephalogram (EEG) has not been routinely utilized in
the evaluation of children with attention deficit hyperactivity disorder
(ADHD). The utility of the EEG in ADHD is unclear. A recent study in
our laboratory using sleep and sleep deprivation routinely found one in
four non-epileptic children evaluated for attention deficit disorder has
epileptiform discharges in the EEG, more than half focal. The majority
of abnormalities (97.5%) occur in sleep and sleep-deprived records
compared to 7% in prior wake only records. A review of eight publica-
tions showed that laboratories using awake only as routine EEG
recordings report a relatively low prevalence of epileptiform dis-
charges, whereas the higher prevalence of epileptiform discharges is
seen in those with more prolonged sleep recordings. We have deter-
mined that sleep deprivation and sleep are essential to rule out an
abnormal EEG in attention deficit disorder.
In patients with attention deficit disorder complicated by epilepsy,
stimulant therapy is generally safe, provided seizures are controlled by
antiepileptic medication. Patients with epilepsy or subclinical electro-
graphic abnormalities not treated with anticonvulsants are at increased
risk of seizures when stimulant therapy is introduced, especially
extended-release methylphenidate. Apart from an increase in risk of
seizures and need for caution in use of stimulants, studies show that
epileptiform discharges in the electroencephalogram are linked to a
better response of attention deficit to methylphenidate and a higher
cognitive performance. Transient cognitive impairment related to sub-
clinical electrographic abnormalities responds to antiepileptic
medication. An EEG is important in selected cases of attention deficit
disorder and is useful in choice of medication, especially in children
with lack of awareness and transient cognitive impairment.
INTRODUCTION
According to the American Academy of Pediatrics Clinical Practice
Guidelines proposed in 2001,1 an EEG is not routinely indicated in the
management of children with ADHD. However, a recent study in our
laboratory employing the sleep deprived EEG finds 1 in 4 children with
ADHD has an epileptiform abnormality.2 The Physicians Desk
Reference3 warns that central nervous stimulants, generally used to
treat ADHD, should be avoided or used with caution in patients with an
abnormal EEG. One in 5 children with epilepsy has ADHD,4 and
children with ADHD have an increased risk of epilepsy.5 A significant
increase in the incidence of seizures is reported during treatment with
methylphenidate in children with ADHD and centro-temporal (rolandic)
spikes in the EEG.6 These warnings and reports of seizure exacer-
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©2011 VOL. 42 NO. 3
bation raise concern about the safety of methylphenidate in children
with a tendency to seizures. The clinical utility of the EEG in ADHD has
been controversial, viewed as limited by some investigators and of
value by others, and needs reappraisal.7,8
In this review, the literature regarding the EEG in the management of
children with ADHD is analyzed; the value of the EEG in determination
of safety of stimulant versus nonstimulant medication in ADHD is dis-
cussed; and the evidence in favor and against antiepileptic drug (AED)
treatment in patients at risk of cognitive impairment is summarized.
Learning disability is a frequent comorbid problem in children with ADHD,
and brief cognitive deficits (transient cognitive impairment) occur in those
patients with subclinical EEG abnormalities.9 Treatment with AEDs may
control EEG epileptiform discharges and benefit cognition in children
with ADHD, a finding that may prompt the reappraisal of the principle of
treating clinical seizures but not the EEG.10
PREVALENCE OF EEG EPILEPTIFORM
ABNORMALITIES IN ADHD
Children with ADHD have a higher rate of EEG epileptiform
abnormalities than the 3.5% reported in healthy controls.11 In our review
of 8 studies of nonepileptic children with ADHD, the prevalence of
epileptiform EEGs varied from 6% to as high as 53%, and an average
of 23.4%.2 The wide range of abnormal records may be attributed to
several factors, including length of recording, sleep, method of
recording (paper or digital), and differences in interpretation. EEGs with
the highest incidence of abnormalities were prolonged and sleep
deprived. In one study of routine, awake EEGs, epileptiform
abnormalities were present in 6.1% of 347 patients. Epileptiform
generalized discharges occurred only in response to activation
procedures, hyperventilation (n=2 patients) and photic stimulation
(n=4); sleep was not obtained and sleep deprivation was not
requested.7 In our laboratory, 26.1% of non-epileptic ADHD patients had
epileptiform EEGs, and more than half had focal discharges, chiefly
central, frontal and temporal.2 Figures 1 and 2 are brief samples of the
kind of focal and generalized epileptiform discharges encountered in
EEGs of our patients with ADHD. The majority of abnormalities (94.5%)
occurred in sleep deprived records and 97.5% were sleep records; only
7% of abnormalities, all generalized, were elicited with hyperventilation
and 10 % with photic stimulation. Of a total of 57 wake-only EEGs, 4
(7.0%) were abnormal, a similar percentage to that reported in a study
that employed wake EEG as a routine.7
From the Division of Neurology (J.G. Millichap, J.J. Millichap, C.V. Stack), Epilepsy Center
(J.J. Millichap) and Neurodiagnostic Electroencephalography Laboratory (C.V. Stack),
Children’s Memorial Hospital, Northwestern University Medical School, Chicago, Illinois.
Address correspondence to J. Gordon Millichap, MD, Division of Neurology, Children’s
Memorial Hospital, 2300 Children’s Plaza, Box 51, Chicago, IL 60614.
Email: gmillichap@childrensmemorial.org
Received: November 26, 2010; accepted: January 18, 2011.
CLINICAL EEG and NEUROSCIENCE
Figure 1.
Representative EEG with focal epileptiform discharges recorded from a non-epileptic 13-year-old boy with ADHD. There are focal spike and slow wave discharges
on either frontal central or central parietal area. Horizontal dipoles were present over each hemisphere. (longitudinal bipolar montage, sensitivity 10 µV/mm, vertical
lines = 1 second.)
A review of 8 published reports of the prevalence of epileptiform
abnormalities reported in nonepileptic children with ADHD2 shows that
those with a relatively low prevalence were awake only or not stated,
whereas the highest prevalence occurred in those with prolonged sleep
recordings. One earlier study employing sleep deprivation12 reported
epileptiform EEG discharges in 30.1% of 176 patients, a relatively high
prevalence similar to that documented in our laboratory.2
RISK OF SEIZURES WITH STIMULANT MEDICATION
The safety of methylphenidate in the treatment of ADHD in children
with epilepsy or EEG abnormalities has been studied only in patients
receiving AEDs in combination with methylphenidate.4 None of 25
children who were seizure free had attacks during methylphenidate
treatment, whereas 3 of 5 children with seizures had an increase in
attacks. Other investigators report the combined treatment safe and
effective in 57 children with ADHD and active seizures and in 62 with
ADHD and EEG abnormalities only.13 Caution is advised in using com-
binations of certain AEDs or antidepressants with methylphenidate; 2
children with ADHD and epilepsy developed severe dyskinesia and brux-
ism when methylphenidate was added to the maintenance valproic acid
therapy.14 Buproprion lowers the seizure threshold and, if used in combi-
nation with methylphenidate, tonic-clonic seizures can be induced.15
Improvements in teacher rating scales of attention and behavior
without recurrence of seizures are reported in 10 children with ADHD
and epilepsy treated with AEDs and methylphenidate.16 The EEG
showed no significant changes of epileptiform features or background
activity in patients who continued psychostimulant therapy, and no alter-
ations in AED levels. Whereas immediate-release methylphenidate in
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©2011 VOL. 42 NO. 3
combination with AED treatment may be safe in the majority of children
with ADHD and epilepsy, the substitution of an extended-release
preparation (OROS-MPH) in increasing doses has been associated with
an increased daily risk of seizures.17 The physician in choosing a medica-
tion for a child with ADHD must weigh the risks and benefits of stimulant,
nonstimulant, immediate-release or extended-release preparations. The
EEG can be of help in arriving at an informed decision.
VALUE OF EEG IN SELECTION OF MEDICATION FOR ADHD
In patients presenting with ADHD, an EEG is not part of the routine
workup. In some circumstances, however, the EEG can be of value in
the selection of medication.2 Patients with episodic altered awareness or
daydreaming, frequent memory lapses, or family history of epilepsy
should be considered for EEG. Activation procedures, especially sleep
deprivation, should be employed to ensure exclusion of EEG seizure dis-
charges and clinical seizure susceptibility.2 When electrographic sei-
zures are uncovered, the non-stimulant, atomoxetine may be considered
as a safer alternative to stimulants and a first choice treatment for ADHD.
If stimulant medication is preferred, the immediate-release preparation is
probably safe in small to moderate doses, and not likely to trigger
seizures.2 Larger doses and extended-release stimulant preparations
should be avoided or used with caution, since seizures are reported,
even in patients treated with AEDs in combination with stimulant.17
SUBCLINICAL ELECTROGRAPHIC SEIZURES
AND TRANSIENT COGNITIVE IMPAIRMENT
A longitudinal follow-up clinical, neuropsychological, and EEG
study of the effectiveness of AEDs in treatment of ADHD and epilep-
tiform discharges showed a temporal relation between subclinical focal
CLINICAL EEG and NEUROSCIENCE
Figure 2.
Representative EEG with generalized epileptiform discharges recorded from a non-epileptic 9-year-old boy with ADHD. There is a brief burst of generalized spike
and slow wave discharges noted during wake without concurrent clinically apparent seizure activity. (longitudinal bipolar montage, sensitivity 20 µV/mm, vertical
lines = 1 second.)
epileptiform discharges and cognitive dysfunction.10 The effect of AEDs
on cognitive impairments should be monitored in addition to seizure
control and reduction in EEG discharges. Transient cognitive impair-
ments involving verbal, visuospatial, and memory function in children
with benign childhood epilepsy with centro-temporal spikes are directly
related to paroxysmal EEG activity.18 Cognitive impairment in children
with ADHD and subclinical spikes in the EEG, described as the under-
recognized epilepsy spectrum, is improved following treatment with the
AED levetiracetam.19
Transient cognitive impairment is reported during generalized
spike-wave bursts for more than 3 sec, and also with focal EEG
discharges.9 Left-sided focal spiking is more likely to be associated
with errors on verbal tasks, whereas right-sided discharges are
accompanied by impairment in nonverbal function. These researchers
concluded that transient cognitive impairment related to subclinical
interictal EEG discharges contribute to learning disabilities in children
with epilepsy. Suppression of discharges by AED therapy may improve
psychological function. Some investigators hypothesize that interictal
spikes, particularly if frequent and widespread, can impair cognitive
abilities by interfering with waking learning and memory and memory
consolidation during sleep.20 The association between interictal
epileptiform discharges and transient cognitive impairment and reports
of improved cognition following AED treatment require further
investigation and confirmation by controlled study.19,21
In contrast to the potential negative effects of methylphenidate in
patients with ADHD and an abnormal EEG, one study using quan-
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©2011 VOL. 42 NO. 3
titative EEG spectral analysis demonstrated normalization of the EEG,
behavior, and cognitive function. Boys with ADHD showed improve-
ments in tasks involving reading, coding, and visual-motor perception
that correlated with regional changes in the EEG.22
COGNITIVE EFFECTS OF ANTIEPILEPTIC DRUGS
Adverse cognitive effects of AEDs23,24 are the chief deterrents to their
usage in non-epileptic children with ADHD complicated by learning
disability. However, a multicenter study of the effects of withdrawal of
AEDs,25 using neuropsychological tests to assess psychomotor function
and cognitive processing, found significant improvements on only one
test, psychomotor speed. The impact of AED treatment on higher-order
cognitive function may be limited and less significant than generally
determined. Impairments persist after drug withdrawal, indicating that the
cognitive impairment attributed to AEDs may be explained partly by the
effects of persisting seizures, especially absence seizures. A decade
later, these investigators concluded that transient cognitive impairment
attributed to interictal epileptiform discharges may sometimes be caused
by short non-convulsive partial seizures or post-ictal effects. Existing
epidemiological data show that the prevalence of cognitive impairment
during epileptiform EEG discharges is low; only 2.2% of patients referred
to a special epilepsy center had episodes of cognitive impairment that
correlated with the EEG discharges.26
Epileptiform EEG discharges in children with epilepsy and psycho-
social-educational problems, and assessed by 24-hour periods of am-
bulatory monitoring, were reduced by AED therapy when compared to
placebo.27 Psychosocial function improved in 8 out of 10 children, and
CLINICAL EEG and NEUROSCIENCE
no cognitive deterioration attributable to the medication was detected.
The investigators conclude that subclinical EEG discharges that impair
psychosocial function can be suppressed by AED treatment.
In a study of the effects of valproic acid in 6 children with EEG dis-
charges and transient cognitive impairment, suppression of epileptiform
discharges improved cognitive performance in only 2. Short epileptiform
subclinical discharges of 10 seconds or less in children with or without
epilepsy will impair reaction time, short term verbal and nonverbal
memory, and school performance in reading, writing, and arithmetic. Fifty
percent of children with subclinical epileptiform discharges show tran-
sient cognitive impairment; those with predominantly left-sided dis-
charges are poor readers while those with right-sided discharges are
poor in performance of visual spatial tasks. The phenomenon of transient
cognitive impairment should be considered when evaluating results of
psychological tests and suspected AED-induced cognitive effects.28
SIGNIFICANCE OF EPILEPTIFORM AND
BACKGROUND ABNORMALITIES IN EEG OF ADHD
Apart from a potential increase in risk of seizures and need for
caution in use of stimulants and some everyday activities such as swim-
ming and sleep habits, epileptiform discharges and EEG background
abnormalities influence outcome of ADHD, response to therapy, and
cognition. A report of EEG abnormalities in children with minimal brain
dysfunction, a former term for ADHD, suggests that EEG and/or neuro-
logical abnormalities (“soft” or “subtle” signs) may predict a better
response to methylphenidate than that in patients with normal EEG and
no neurological soft signs.29 Also, both epileptiform discharges and EEG
background abnormalities are linked to higher measures on cognitive
performance tests in hyperactive children,30 findings determined to be
consistent with a neurobiological and maturational basis for ADHD.
A quantitative EEG study in ADHD that analyzed the relative power
in delta, theta, alpha, and beta bands found 3 distinct clusters with
differences in slow and fast activity in frontal, central, and posterior
regions. The EEG frequency clusters correlated with clinical subtypes,
a finding suggestive of a heterogeneous disorder with different under-
lying electrophysiological abnormalities.31 In a further quantitative EEG
study of 100 patients with attention deficit disorder, background activ-
ities (frontal alpha or theta excess, or inter-hemispheric incoherence)
are correlated with response to stimulant or anticonvulsant treatment
and with clinical outcome.32
The risk of seizures correlating with an epileptiform EEG varies
with individual patients and their inherent susceptibility. One report and
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The prevalence of epileptiform discharges in the EEG of non-
epileptic children with ADHD is at least 6-fold greater than in a healthy
population without ADHD. Patients with episodic altered awareness,
frequent daydreaming or memory lapses should be considered for
EEG. If a tendency to seizures is suspected in a child with ADHD, a
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EEG in ADHD should be modified to specify the indications and
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The EEG may be of value in selection of medication for the treatment
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choice of stimulant (immediate- or extended-release) or non-stimulant
treatment, EEG findings may lead to a trial of an AED in the absence of
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ment may be important in the evaluation of AEDs and significance of
cognitive effects.
This review and analysis of the utility of the EEG in the management
of ADHD was prompted by our recent report of the importance of sleep
deprivation and ineffectiveness of a routine wake EEG in prediction of
seizure susceptibility in these patients.2 In view of the frequency of
epileptiform abnormalities demonstated in our study and that of others12
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cation to include AED treatment of the epileptiform discharge.
DISCLOSURE AND CONFLICT OF INTEREST
J. G. Millichap, J. J. Millichap and C. V. Stack have no conflicts of
interest in relation to this article.
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