Epilepsy & Behavior 41 (2014) 251–256

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Epilepsy & Behavior

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Reappraisal of abnormal EEG findings in children with ADHD: On the

relationship between ADHD and epileptiform discharges
Osamu Kanazawa 1,⁎
Department of Neuropsychiatry and Psychosomatic Internal Medicine, Saitama Medical University, 38 Morohongo, Moroyama-cho, Iruma-gun, Saitama Prefecture 350-0495, Japan

a r t i c l e i n f o a b s t r a c t

Article history: Introduction: Attention-deficit hyperactivity disorder is suggested to be closely related to epilepsy. A recent
Received 11 June 2014 large-scale study revealed that ADHD in children is often accompanied by epilepsy. In Japan, methylphenidate
Revised 8 September 2014 (MPH) as a sustained-action tablet and atomoxetine (ATX) became commercially available as medications for
Accepted 28 September 2014 children recently. Since then, the number of prescriptions of both medicines has increased rapidly. Methylphe-
Available online xxxx
nidate, as a psychostimulant, has been a source of concern because of the perceived lowered threshold for con-
vulsions in children. Based on this background, reappraisal of EEG findings in children with ADHD is important
Keywords:
Attention-deficit hyperactivity disorder (ADHD)
in order to detect indications of potential comorbid epilepsy and to investigate the developmental mechanisms
Electroencephalography (EEG) of the neurophysiological manifestations in patients with ADHD.
Epileptiform discharge Material and method: EEG findings in children newly diagnosed with ADHD and their relationship with clinical
Epilepsy findings were investigated. The author evaluated 208 patients with ADHD newly diagnosed between 2008 and
Autism spectrum disorder (ASD) 2013. Of these, there were 145 patients for whom EEG findings were obtained along with a clinical follow-up
for at least three months. Patients with IQ b 70 were excluded in order to obtain a homogenous group of patients
with ADHD. The male-to-female ratio was 130:15, and the age range was between 5 years, 9 months and
19 years, 9 months, with mean age of 11 years, 4 months.
Results: The results revealed that about half (48.3%) of the children with ADHD had abnormal EEG findings and
that 22.1% of them had epileptiform discharges. Patients without comorbidity of autism spectrum disorder (ore
homogenous group with ADHD) were especially likely to show abnormal EEG findings (51.0%) including epilep-
tiform discharges (24.5%). Afebrile seizures, that is, epileptic seizures, occurred in a boy three days after com-
mencement of administration with MPH as a sustained-action tablet. In four patients with a past history of
epilepsy, neither relapse of EEG abnormality nor epileptic seizures were observed during the follow-up period.
Conclusion: There was to be a significantly close relationship between ADHD and epileptiform discharges. There-
fore, in patients with ADHD, it is important to obtain more precise information about seizures and presence of ep-
ilepsy from the personal and family histories, as well as to undertake a thorough EEG examination.
© 2014 Elsevier Inc. All rights reserved.

1. Introduction as ADHD. It is well recognized that the relationship between these

It was been suggested that there is a close relationship between at-
tention-deficit hyperactivity disorder (ADHD) and epilepsy [1,2]. Re-
cently, it was reported that the number of patients diagnosed as
having ADHD during childhood and adolescence has been increasing
[3–5]. Alternatively, epilepsy occurring during childhood and adoles-
cence is one of the functional disorders of the central nervous system
and is a chronic disease that was previously recognized as the most
common morbidity (0.5–1.0%) [6].
In terms of the subdivision of developmental disorders, there are
learning disorder (LD) and autism spectrum disorder (ASD), as well
⁎ 2-7-29 Isehara-cho, Kawagoe City, Saitama Prefecture 350-1108, Japan. Tel.: +81 49
276 1214; fax: +81 49 276 1622.
E-mail addresses: kanaosa@saitama-med.ac.jp, kanaza38@nifty.com.
1
Tel./fax: +81 49 231 5445.
developmental disorders and epilepsy, particularly between ADHD
and epilepsy, is very close, which is supported by evidence including re-
search with animal models [1,2,6–10].
About 35% of children with ADHD show abnormal EEG findings, and
Socanski et al. [9] demonstrated that thirty-nine (7.5%) patients among
a total of 517 children with ADHD showed epileptiform discharges on
their EEGs. In addition, they [10] reported that fourteen (2.3%) patients
had epilepsy among 607 children with ADHD. In Japan, in spite of many
researchers reporting high incidences of cases showing comorbidity
with ADHD in children with epilepsy, there are few reports of comorbid
epilepsy in children with ADHD. In 2007, methylphenidate (MPH) as a
sustained-action tablet and, in 2010, atomoxetine (ATX) became com-
mercially available as medications for children. Since then, the number
of prescriptions for MPH and ATX has increased rapidly. Methylpheni-
date has been associated with a concern about a lowered threshold for

http://dx.doi.org/10.1016/j.yebeh.2014.09.078
1525-5050/© 2014 Elsevier Inc. All rights reserved.
252 O. Kanazawa / Epilepsy & Behavior 41 (2014) 251–256
convulsions in children, which was supposed to be due to MPH possibly
being a psychostimulant. Against this background, reappraisal of EEG
findings in children with ADHD is important in order to make a diagno-
sis and therapeutic strategy and to investigate the developmental
mechanisms of the neurophysiological manifestations in patients with
ADHD [11–14]. The author examined EEG findings in children newly di-
agnosed with ADHD and investigated their relationship with clinical
findings.
2. Material and method
The study design was prospective, in which patients with ADHD as
the most serious clinical symptom as well as social problem were select-
ed. Prior to initiation of medical treatment, EEG examination and clinical
history including seizure episodes were obtained in every new patient.
However, because of their negative opinion of epilepsy and EEG abnor-
malities, several patients or their parents would not allow EEGs to be
performed.
In order to prevent or minimize comorbidity of the other develop-
mental disorders, patients with intellectual disability were excluded,
that is, patients with intelligence quotient (IQ) or developmental
quotient (DQ) below 70. Probably because of that IQ definition, patients
with cerebral palsy were not included in the final cohort. Nevertheless,
mild types of ASD were not excluded. Therefore, in this study, EEG find-
ings and epileptiform discharges were investigated and compared be-
tween two groups (patients with ADHD without ASD vs. patients with
ADHD with ASD). Finally, EEG findings and epileptiform discharges
were investigated and compared between the two gender groups.
The author evaluated 208 patients with ADHD newly diagnosed be-
tween 2008 and 2013. Of these, there were 145 patients who were clin-
ically followed up for at least three months and from whom
EEG findings were obtained. The male-to-female ratio was 130:15
(Fig. 1A), and the age range was between 5 years, 9 months and
19 years, 9 months, with mean age of 11 years, 4 months.
The data on these subjects were obtained from the following four
institutes: Clinic of Children's Psychiatry in Kawagoe Clinic, Saitama
Medical University; Clinic of Children's Psychiatry in an outpatient
clinic, Department of Neuropsychiatry and Psychosomatic Internal
Medicine, Saitama Medical University; Clinic of Pediatric Neurology in
Himawari Educational Institute, Comprehensive Center of Education
harmonized with the medical services of Saitama City; and Outpatient
Clinic of Pediatric Neurology in the Sanatorium Institute of Saitama
Education harmonized with the medical services.
The diagnosis of ADHD was based on DSM-IV, and in principle, pa-
tients with an ADHD-RS-IV score under twenty were excluded. In
addition, patients with epilepsy in advance of an ADHD diagnosis were
excluded. However, such patients were included in this study if they
had a past history of epilepsy that was regarded as completely remitted
and if the use of antiepileptic drugs had ceased more than three years
ago. It has recently become apparent that determining ADHD subtypes
A. The gender ratio
in 145 patients
N=15 (10.3%)
N=14
(9.7%
Male
Female
N=130 (89.7%)
Fig. 1. A: The ratio of the genders. B: The details of administration in 145 patients.
(inattentive type, hyperactive-impulsive type, and combined type) is
not clinically useful because of the change of the predominant symp-
toms with aging, unstable symptoms in patients due to the develop-
mental stage, and almost equally favorable response to neurostimulant
medication [15]. Therefore, the author did not attempt to determine
the subtypes of ADHD.
Generally, more than one EEG examination was undertaken before
the commencement of medication. However, a few patients underwent
EEG immediately after the commencement of medication. In addition,
EEG was usually recorded during both wakefulness and sleep, and if
necessary, a hypnotic drug was administered in order to record sleep
EEG. Electroencephalography was taken using the international 10–20
method, and the relationship between EEG findings and clinical
symptoms including epileptic seizures was investigated. EEGs were
interpreted by two individuals: one is the author, who is a certified spe-
cialist of the Japanese Society of Clinical Neurophysiology, and the other
is a clinical laboratory technician, who is also an expert in the field of
neurophysiology. In addition, the incidences of abnormal EEG findings
and epileptiform discharges were compared and examined between pa-
tients with and those without comorbid ASD. Furthermore, those inci-
dences were also compared and examined between the genders. If the
patient had a past history of epilepsy or if the initial EEG showed abnor-
mal findings, EEG examination was repeated every half year.
None of the results reached statistical significance; therefore, the re-
lated p values are not shown.
3. Results
3.1. Medication for ADHD
The medications for ADHD in the 145 patients were as follows: MPH
as a sustained-action tablet alone in 83 (57.2%) patients, ATX alone in 26
(17.9%) patients, both MPH and ATX in 14 (9.7%) patients, and antiepi-
leptic drugs or drugs other than MPH or ATX in addition to MPH or
ATX in 4 (2.8%) patients. The number of patients with no medication in-
cluding previous MPH or ATX administration was 18 (12.4%) (Fig. 1B).
3.2. EEG findings in 145 patients
Among the total of 145 patients, 70 (48.3%) showed abnormal EEG
findings, and of them, 32 (22.1%) showed epileptiform discharges. Of
these 32 patients, generalized discharges appeared in 6, and focal dis-
charges appeared in 23, and both generalized and focal discharges ap-
peared in three patients. Focal discharges appeared in the frontal area
in 7 patients, central area in 11 patients, temporal area in 2 patients, pa-
rietal area in 3 patients, occipital area in 7 patients, and more than one
area in a few patients. There were other EEG findings: slow alpha activ-
ities appeared in 27 (18.6%) patients, and asymmetrical alpha activities
appeared in 19 (13.1%) patients. These alpha activities were mainly
asymmetrical in terms of amplitude and less commonly in terms of
B. The details of
N=18 administration
N=4 (12.4%) in 145 patients
(2.8%)
MPH
ATX
MPH & ATX
N=26 N=83 Other medicaon
(17.9%) (57.2%)
No medicaon
 O. Kanazawa / Epilepsy & Behavior 41 (2014) 251–256 253

A. EEG findings B. Epileptiform discharges

in 145 patients
in 145 patients Abnormal
N=32
Normal (22.1%)

Yes
No
N=75 N=70
(51.7%) (48.3%) N=113
(76.8%)

Fig. 2. A: EEG findings in 145 patients. B: Epileptiform discharges in 145 patients.

frequency. Right-side-dominant asymmetry (higher right-side alpha) patients, and epileptiform discharges were found in 3 (20.0%) patients
appeared in 12 (63.2%) patients, left-side-dominant asymmetry (higher (Figs. 4A, B). The patient in whom epileptic seizures occurred was
left-side alpha) appeared in 6 (31.6%) patients, and the laterality was male (see Case report).
unknown in one patient (Figs. 2A, B).
Four patients had a past history of epilepsy (their seizures had remit-
3.5. Case report
ted, and they were free from antiepileptic drugs for over three years),
and nine (6.2%) patients had a past history of febrile convulsion (FC).
Of the six patients who showed generalized epileptiform discharges,
Of the four patients with a past history of epilepsy, two showed epilep-
one (16.7%) patient exhibited episodes of afebrile seizures consisting of
tiform discharges in the premedication EEG examinations (multifocal
disturbed consciousness. A brief case report of this patient is provided
spike discharges and generalized 3-Hz spike–wave discharges, respec-
below.
tively). Those epileptiform discharges were unchanged in the follow-
A 12-year-old male patient visited the author's clinic at the age of
up study, and no relapse of seizures occurred during the follow-up peri-
8 years because his schoolteacher had recommended that he see a spe-
od. Of the nine patients with FC, seven patients had had more than one
cialist physician due to his restlessness during school hours. He had a
seizure.
past history of FC with 6 or 7 convulsive seizures, and his IQ was 88.
Of the six patients showing generalized discharges, one patient ex-
He had a convulsive seizures in paternal kindred, but without detailed
hibited afebrile seizures, that is, epileptic seizures, during ADHD therapy
information. In his EEG, 3-Hz spike–wave discharges appeared with
with MPH (see Case report). The manifestation of the seizure episode
dominance in the frontal area during wakefulness, and diffuse 2-Hz
was loss of consciousness, which was regarded as an absence seizure.
spike–wave discharges appeared with dominance in the frontal area
during sleep. He had some prodromal sensations of seizures since com-
3.3. Comparison between the patient group with (group A) and the patient mencement of MPH as a sustained-action tablet at 18 mg and diagnosed
group without (group NA) ASD as afebrile seizures consisting of episodes of loss of consciousness and a
possible convulsion that occurred three days after the initiation of MPH
The number of patients in group A was 43 (29.7%), and that in group medication. Since stopping MPH, he had been free from seizures in spite
NA was 102 (70.3%). Abnormal EEG findings were found in 18 (41.9%) of no administration of antiepileptic drugs (Fig. 5).
patients in group A and in 52 (51.0%) patients in group NA (Fig. 3A).
Epileptiform discharges were found in 9 (20.9%) patients in group A
4. Discussion
and in 25 (24.5%) patients in group NA (Fig. 3B). Afebrile convulsions
or episodes of disturbed consciousness, that is, epileptic seizures, oc-
4.1. Increasing rate of ADHD and its strong association with epilepsy
curred in a patient in group NA (see Case report). Patients with epilepsy
as past history were more common in the group without ASD (three vs.
Attention-deficit hyperactivity disorder is a form of develop-
one).
mental disorder that is characterized by the principal symptoms of
inattentiveness, hyperactivity, and emotionality; it has become recog-
3.4. Comparison between the genders nized as becoming conspicuous during childhood and adolescence.
By contrast, epilepsy is a chronic disease characterized by spontaneous
In the 130 male patients, an abnormal EEG was found in 64 (49.2%) and repetitive seizures as the principal symptom, and most such patients
patients, and epileptiform discharges were found in 29 (22.3%) patients. show paroxysmal discharges (epileptiform discharges) on their EEG and
In the 15 female patients, an abnormal EEG was found in 6 (40.0%) may also exhibit various other symptoms due to cerebral dysfunction.

A. EEG findings B. Epilepform discharges

Group N=18 (41.9%) N=9 (20.9%)

A Group A

Group N=25
N=52 (51.0%)
Group NA (24.5%)
NA Yes
Abnormal
No
0 100 200 Normal 0 50 100 150

Fig. 3. Comparison between group A (N = 43) and group NA (N = 102). A: EEG findings. B: Epileptiform discharges. Group A = with ASD; Group B = without ASD.
254 O. Kanazawa / Epilepsy & Behavior 41 (2014) 251–256

A. EEG findings B. Epileptiform discharges

N=29
N=64 (49.2%) Male
Male (22.3%)

N=6 (40.0%) N=3 (20.0%)

Female Abnormal Female
Yes
Normal
No
0 100 200 0 50 100 150

Fig. 4. Comparison between the genders (male:female = 130:15). A: EEG findings. B: Epileptiform discharges.

Formerly, epilepsy was regarded as the most common chronic neuro-
logical disease, and its rate was generally estimated to be 0.5–1.0% as the
maximum rate in childhood. Outside of Japan, the rate of developmental
disorders is reported to be increasing. Several studies have estimated in-
creasing and, particularly, high rates of ADHD in childhood in contrast
to the constant comorbidity rate of epilepsy in childhood. According to a
large-scale survey in Norway, the rate of ADHD in children at the age of
11 years was 2.9%, with over fourfold predominance in boys [3]. In
Israel, the rate of ADHD from a national survey was surprisingly as high
as 12.6%, and ADHD was reported to be the comorbidity in 27.7% of chil-
dren with epilepsy [4]. In addition, the risk of developing epilepsy in chil-
dren with ADHD was about twofold higher than that in children without
ADHD. Nonetheless, in Japan, such large-scale nationwide surveys have
not yet been undertaken. The recent apparent increase in the number of
children with ADHD seems to suggest that these trends are also prevailing
in children in this country. Incidentally, in 2002, the Japanese Ministry of
Education carried out a questionnaire survey for schoolteachers on the
national scale, in which they were asked how many students were in
need of special educational support in ordinary classes. According to the
results of this survey, the supposed rate of ADHD in children of school
age was 2.5%.
4.2. Comorbidity of epilepsy and ADHD
Formerly, it was reported that 30–40% of children with epilepsy had
ADHD, while 5–60% of children with ADHD had epileptiform discharges
on their EEGs, and 10–20% of them were diagnosed as having
epileptiform discharges [1,2]. It is, thus, suggested that epilepsy and
ADHD may be two different independent expressions of a common neu-
robiological abnormality.
About 70% of patients with frontal lobe epilepsy (FLE) have ADHD
and there is an especially high affinity between ADHD and FLE [16,17].
Children with childhood absence epilepsy (CAE) are prone to the co-
morbidity of inattentive-type ADHD [18]. Moreover, it has been report-
ed that symptoms of ADHD have a close relationship with benign
epilepsy of childhood with centrotemporal spikes (BECT), rolandic
discharges (RD), or Panayiotopoulos syndrome [19].
In addition, it has been proposed that there is a relationship between
sleep disorder in patients with epilepsy and ADHD, and worsening by
adverse effects of antiepileptic drugs such as phenobarbital, benzodiaz-
epines, and topiramate has also been suggested [1].
4.3. Comparison of numerical values between the present research and
previous reports
In the present research, about half (48.3%) of the 145 patients with
ADHD showed abnormal EEG findings, and approximately half (22.1%)
of the abnormalities involved epileptiform discharges. According to
these results, abnormal EEG findings and epileptiform discharges were
found in patients with ADHD at a high rate, which is close to the median
value in the previous reports (5–60%); it appears that the relationship
between ADHD and epilepsy is strong. While Socanski et al. [9] reported
that 39 (7.5%) patients among a total of 517 patients with ADHD
showed epileptiform discharges, the present study reveals an incidence

Fp1-A1
Fp2-A2
F3-A1
F4-A2
C3-A1
C4-A2
P3-A1
P4-A2
O1-A1
O2-A2
F7-A1
F8-A2
T3-A1
T4-A2
T5-A1
T6-A2
EOG
ECG

During wakefulness During sleep

Fig. 5. EEG in the case report. EEG at 8 years of age before commencement of medication showed diffuse 3-Hz spike–wave discharges during wakefulness and 2-Hz spike–wave discharges
during sleep.
 O. Kanazawa / Epilepsy & Behavior 41 (2014) 251–256
over three times higher. One reason for this high incidence may be that
the author is a specialist certified by the Japan Epilepsy Society, so there
may be some bias in terms of patients evaluated at the author's outpa-
tient clinic. Another reason may be that the analytical sensitivity for ep-
ileptiform discharges has increased because of sufficiently long EEG
recording, including during both wakefulness and sleep.
Despite focal discharges being found in more patients who showed
epileptiform discharges, one patient in whom epileptic seizures oc-
curred during follow-up showed generalized epileptiform discharges.
Concerning the localization of these focal discharges, the number of
patients who showed central discharges was the greatest, that is,
about half of the total, followed by patients with frontal and occipital
discharges as the next two largest groups. According to these results,
it is possible that most focal discharges have characteristics in common
with such focal discharges as found in benign partial epilepsy in
children.
As abnormal EEG findings other than epileptiform discharges, slow
alpha activities were found in 18.6% of patients with abnormal EEG,
and asymmetrical alpha activities were found in 13.1% of patients.
These results suggest immaturity of the brain and imbalanced brain
maturation in patients with ADHD [20]. Detailed description of other
EEG findings is beyond the scope of this report.
Forty-three (29.7%) patients out of the total of 145 had the comor-
bidity of ASD. While patients without ASD showed more frequent ab-
normal EEG findings and epileptiform discharges than patients with
ASD, there was not a statistically significant difference. In this study,
the patient group without comorbid ASD must be regarded as the core
group or the group with pure ADHD. The reason for the less frequent ep-
ileptic discharges in the patients with ASD may be the IQ or DQ being
above the normal level (IQ or DQ N 70) of the population in this
study. Although patients with ASD also have the comorbidity of epilepsy
[21], recently, it has been reported that patients with normal or mildly
low IQ also have epilepsy less frequently, and epilepsy may be particu-
larly closely related to intellectual disability in ASD [22]. In the present
study, the patient who had seizures during follow-up did not have ASD.
Although the number of female patients was only 15 (10.3%), they
showed less frequent abnormal EEG findings and epileptiform
discharges than male patients. However, there again was no statistically
significant difference. According to the results from 517 patients
with ADHD reported by Socanski et al. [9], epileptic discharges were
found more frequently in female patients, especially in those with
inattentive-type ADHD.
4.4. A patient in which epileptic seizures occurred during the follow-up
period
Although only one patient had seizures during treatment, this clini-
cal experience is informative regarding the treatment of ADHD with
MPH. This patient in which afebrile seizures occurred during ADHD
therapy had a past history of FC, convulsive disease as family history,
and generalized epileptiform discharges on EEG examination before
ADHD therapy. Generalized epileptiform discharges in this patient
consisting of diffuse 3-Hz spike–waves predominantly in the frontal
area, which are characteristic of epileptiform discharges seen in idio-
pathic generalized epilepsy. A patient with ADHD having those predis-
posing epileptiform discharges and FC as past history or convulsive
disease as family history should be considered to be at risk for convul-
sive seizures. Therefore, it is necessary to pay attention to such patients
during ADHD therapy, including the possibility of seizures induced by
medication for ADHD. Socanski et al. [10] reported that, in 607 patients
with ADHD, fourteen (2.3%) had the comorbidity of epilepsy.
In this patient, a convulsion occurred on just day three of medica-
tion. Given this serious outcome, MPH seems to have rapidly lowered
the threshold for convulsion. Methylphenidate is categorized as a
neurostimulant, and there are some reports of convulsion caused by
MPH in children with ADHD [23]. However, there do not seem to be
255
any reports on MPH being a statistically significant inducer of convul-
sions. Generally, both MPH and ATX seem not to convey any additional
risk of seizure aggravation when administered to patients with both
ADHD and epilepsy [24–26]. Nevertheless, if patients with ADHD have
a past history of FC, a predisposition to generalized epileptiform dis-
charges, and a family history of convulsive disease, they and their
guardians should be informed of the risk of seizures before drug therapy
for ADHD is started.
4.5. Medical treatment for comorbidity of epilepsy
Epilepsy and ADHD may be two different independent expressions
of a common underlying neurobiological abnormality. There are several
reports supporting this hypothesis [13,27–29]. The improvement of ep-
ileptic seizures or abnormal EEG findings associated with ADHD also
may result in improved ADHD symptoms. In addition, it has been sug-
gested that LEV may be a beneficial for ADHD symptoms [28].
4.6. Future prospects of medical care for ADHD and developmental disorders
Recently, the prevalence of developmental disorders, especially
ADHD and ASD, has been increasing worldwide [3–5]. Supposing that
there is a common pathophysiological basis for both ADHD and epilep-
sy, how should we explain the increasing prevalence of ADHD but not of
epilepsy? If ADHD symptoms are assumed to be a risk factor for epilep-
sy, it may be conceivable that ADHD may precede epilepsy by a number
of years.
The present study showed that it is highly possible that a predispo-
sition to epilepsy is closely related to ADHD. Given this finding, the safe-
ty of MPH and ATX for the treatment of ADHD should be further studied.
In fact, the increasing focus on the use of MPH and ATX as treatment
in patients with ADHD for the symptoms of ADHD, perhaps enhanced
by increased awareness of the disorder, may be deflecting attention
away from searching for causes of the increasing incidence of ADHD
and further exploration of EEG findings [30].
5. Conclusion
This study has shown that about half of patients with ADHD showed
abnormal EEG findings and that almost a quarter of patients showed
epileptiform discharges. Epileptic seizures occurred in one patient in as-
sociation with MPH treatment. The findings of this study support a close
relationship between ADHD and epileptiform discharges. Therefore,
personal and family histories of seizures and epilepsy should be sought
in the workup of patients with ADHD and thorough EEGs should be ob-
tained when indicated. Additional studies are needed to confirm the
findings of this study.
Conflict of interest
There is no conflict of interest with any pharmaceutical companies,
any other institutes, or any authors.
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