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British Journal of Psychiatry (1994), 164, 528—532

Prevalence and Associated Features of Epilepsy in


Adults with Down's Syndrome
R. W. McVICKER, 0. E. P. SHANKS and A. J. McCLELLAND

The aim of this study was to establish the prevalence of epilepsy in persons with Down's
syndrome aged 19 years and over. A total of 191 adults with Down's syndrome were identified,
giving a prevalence of 0.76/1000(95% Cl 0.75 to 0.77). Of these, 18 had epilepsy, giving
a prevalence of 9.4% (95% Cl 5.3% to 13.5%). The prevalence of epilepsy increased with
age, reaching 46% in those over 50. The neurophysiological (EEG) findings of the epilepsy
group were compared with those of a control group of Down's syndrome adults without
epilepsy. Paroxysmal abnormalities consistent with a diagnosis of epilepsy were found in 80%
of the epilepsy group, compared with only 13% of controls (P'zO.OOl). Epilepsy of late onset
was associated with diffuse EEG abnormalities and clinical evidence of dementia. The age
distribution and EEGfindings suggest two independent processes in the causation of epilepsy:
late-onset epilepsy associated with clinical evidence of dementia, and early-onset epilepsy
in the absence of dementia.

Down's syndrome is a common cause of mental bimodal distribution in the age of onset of seizures.
handicap, with an incidence of approximately one These findings were made possible due to the
in 700 registered births (Department of Medical increased life expectancy of people with Down's
Genetics, Queen's University, Belfast). Epilepsy is syndrome. Carter & Jancar (1983) demonstrated an
a significant cause of secondary handicap in the increase in life expectancy of 40 years over the period
mentally handicapped population and, in spite of 1930—80.
previous reports to the contrary, is now being A further consequence of the increased longevity
recognised as an important cause of morbidity in has been the increasing number of reports of
Down's syndrome. Alzheimer's disease in patients with Down's syn
The early literature on Down's syndromedoesnot drome. Since the early work of Jervis (1948),
refer to epilepsy at all. Epilepsy was not included in numerous studies have reported the association
Langdon Down's description of the syndrome over between Down's syndrome and Alzheimer's disease
100 years ago (Langdon Down, 1866). Major (Olson & Shaw, 1969; Wisniewski ci a!, 1985;
textbooks a quarter of a century ago stated that Oliver & Holland, 1986; Zigman ci a!, 1987; Cork,
epileptic seizures were not observed in Down's 1990; Evenhuis, 1990). In an extensive survey of
syndrome (Slater & Roth, 1969). Studies of the autopsy data for adults with Down's syndrome,
prevalence of epilepsy in Down's syndrome have Schweber (1989) found that brain neuropathology
reported rates varying from 1°loto 14% (Kirman, of Alzheimer's disease was universal in those aged
1951;yeah, 1974;Romano et al, 1990;Pueschelet al, 37 and over. Several workers have noted that epilepsy
1991). MacGillivray (1967) reported a prevalence rate of late onset was associated with the neuropatho
of 8% in a hospital population of 111 Down's logical changes of Alzheimer's disease (Olson &
syndrome patients, over a ten-year period. Signifi Shaw, 1969; Miniszek, 1983; Oliver & Holland, 1986;
cantly, MacGillivray questioned the traditional Lai & Williams, 1989; Evenhuis, 1990).
concept of the rarity of epilepsy in Down's syndrome The aim of the present study was to establishthe
and claimed that the notion that Down's syndrome prevalenceand the associatedfeatures of epilepsyin
actually protected against epilepsy was erroneous. personswith a diagnosisof Down's syndrome, aged
These studies, however, were based on selected and 19 years and over, residing within (community
therefore biased population samples (MacGillivray, residents) or originating from (hospital in-patients)
1967;Veall, 1974;Tangye, 1979;Romano et al, 1990; the Belfast catchmentarea of the Eastern Health and
Pueschel ci a!, 1991). Social Services Board, Northern Ireland.
Veall (1974) in his study of 1654 patients with
Down's syndrome showed an increased prevalence
Method
of epilepsy with increasing age (1.9% under 20 years
and 12.2% over 55 years). Veall also suggested a The selection criteria were as follows:

528
EPILEPSYIN ADULTSWITHDOWN'SSYNDROME 529

(a)diagnosis of Down's syndrome(this was a clini 5.3—l3.5°lo).


Thosewithepilepsy wereon average9 years
cal diagnosis, as it was not possible to confirm the older than those without (P<0.OOl). The prevalence of
diagnosis by chromosome analysis in all cases) epilepsy among those living in the community was 6°lo,
(b)age19years andover, i.e.theageofcommencement comparedwith26%forthosein hospital(P<0.001). The
of attendance at adult training centres agedistribution
oftheepilepsy
group(n= 18,meanage44
(c) residents from the Belfast catchment area, with an years) was significantly skewed in comparison with that of
estimated adult population of over 250 000. the non-epilepsy
group (n= 173,mean age 35 years)
(P<0.001)(Fig.
1).Inthoseunder50,theprevalence
of
In-patientsof MuckamoreAbbey Hospital, whose home epilepsy was 7%, compared with 46% in those aged 50 years
addresses were within the Belfast catchment area, were also
and older(P<0.OOl).
included. Muckamore Abbey is the specialist mental
handicaphospitalserving
thepopulation oftheEastern
Health and Social Services Board. The medical file was the Clinical characteristics of epilepsy
main source of the clinical and demographic data. Epilepsy
was basedon clinical
evidence
and was diagnosed
ifone Thereportedseizuretypewasgeneralisedtonic-clonicin
or more seizureshad occurred during the two years prior
17patients.
Two in-patients hadanaverage ofoneseizure
to the study,or ifthe subject had been on regular per month, five had less than one seizure per month and
anticonvulsant therapy for seizures occurring earlier. two were seizure-free.Three of thoseliving in the
Electroencephalographic(EEG) evidence was sought in all communityhad less thanone seizureper month,and six
cases to assist in the classification of seizures, using the
wereseizure-free.
Anticonvulsant therapy wasprescribed
International League Against Epilepsy classification of for 15patients,14of whomwereon monotherapy.Sodium
seizure
type(1981). ina group valproate was prescribed for eight patients and was
EEGs werealsoevaluated
of 15 control subjects without epilepsy, matched for age.
combinedwithphenytoinin one patient.Carbamazepine
Themeanageoftheepilepsy
groupatthetimeoftheEEG was prescribedfor six patients.Regularmonitoringof serum
investigation
was40years(range comparedwith antiçonvulsant
20—59), levels was carriedoutinmostpatients.
a meanageof43years
(range21-65)
forthecontrol
group.
Age of onset
In two (11%) patients epilepsy began before 19 years of
Screening
age(childhoodepilepsy); ineight (45%)onset wasbetween
Screeningconsisted adultswithDown's 20 and 29 years(youngadultonset), in one at 36 years,
of identifying
syndromeattending
adulttraining
centres thedefmed in threebetween40 and49 years,in threebetween50 and
within
catchmentarea,and usingtheSocial
Services to 59 yearsand in one at 63 years(late-onsetepilepsy).
register
identify
thoseadults
withDown'ssyndromenotattending
adulttraining
centres. team(RMcV) Developmental regression
One oftheresearch
recordedon a formtheage,sex,placeofresidence,
and In the six adultswithepilepsyunderthe age of 35 years,
details of the diagnosis of epilepsy: age at onset, type and
no developmentalregressionwas noted. Of the 12 adults
frequency of seizures, anti-epileptic drugs and EEG
withepilepsyovertheageof 35years,eight(67%)showed
investigations. Developmental regression was noted to be
clinical evidence of developmental regression. The high
present if significant deterioration in the subject's cognitive
and behavioural skills had been observed during the two
years before the time of the study. 70

Results 60

I
Prevalence
ofDown'ssyndrome 50
The number of adults with a diagnosis of Down's syndrome
inthepopulation
studied
(total
numberofadults inthe 40
catchment
area,250000:see(c),
above)was 191,giving
a prevalence rate of 0.76 per 1000 (95tVoCI 0.75—0.77):37°lo 30
ofthepopulation with Down's syndromewerebetween l9and
29years;33%werebetween30and39years;22%werebetween 20
40and49years
and8% over50years.
Thereweresignifi
cantdifferencesbetweentheagedistributionof thesample 10
living in the community (n = 157, mean age 33.5 years) and
the hospital sample (n = 34, mean age 54.5 years) (P<0.OOl). 0
18—29 30—39 40-49 50—59 60-69
Prevalence of epilepsy In Down's syndrome Age:years
Eighteen adults with Down's syndrome satisfied the criteria Fig. I Numbers of Down's syndrome subjects with and without
for epilepsy, giving a prevalence rate of 9.4010 (95% CI epilepsy (@ no epilepsy, •¿epilepsy).
530 McVICKER ET AL

prevalence of epilepsy in the 50 + age group has already The prevalence of epilepsy in adults with Down's
been noted. Of the 15 adults over the age of 50, syndrome was 9.4% , and, based on the EEG
developmental regression was reported in all seven with evidence, the epilepsy was of partial type in most
epilepsy and in only one without epilepsy (P=0.06). cases (ILAE, 1981). This study shows that the
prevalence of epilepsy increased with age, being
Neurophysiological findings
particularly high (46%) in those over the age of 50
Interictal EEGs were obtained in 15 of the 18 patients with years. It was also higher (26%) among hospital
epilepsy. Two patients were uncooperative and one was too in-patients. While hospital in-patients were generally
frail to have an EEG performed. Paroxysmal abnormalities older than community patients, neither age nor
consistent with a diagnosis of epilepsy were noted in 12
epilepsy accounted for the reason for admission to
(80%)patientswithepilepsycomparedwithonlytwo (l3°bo)
controls (sensitivity of 80°boand specificity of 87Sbo,
hospital. Two patients had been admitted for clear
P<0.OOl). Of the 12 adults in the epilepsy group with medical reasons in the previous 12 months, both
paroxysmal abnormalities, six showed a temporal lobe focus women in their SOswith a diagnosis of dementia.
and three showed a parietal lobe focus. The other seven had been in-patients for an average
Of the 10 adults in the epilepsy group over 35 years, eight of 20 years (range 11—37),whose age at the time of
(80°lo)had diffuse abnormalities consistent with a clinical admission was on average 31 years (range 11—48).
diagnosis of dementia. Six (75°bo)of these showed clinical The majority of these were admitted because carers
evidence of developmental regression (P= 0.06). Of the 11 were unable to cope for various reasons, including
adults in the control group over 35 years, only one (9%)
severe behaviour problems.
showed diffuse abnormalities. No such EEG abnormalities
were evident in those under 35 years in either the epilepsy
The manifestations of an epileptic seizure may
orthecontrol group. include complex abnormalities of behaviour and
subjective experience (Fenton, 1986). The diagnosis
Classification and classification of epilepsy can therefore be more
difficult in the mentally handicapped population,
As regards classification of seizure type, the clinical and
EEG evidence was consistent with partial seizures evolving
given the limited cognitive and communication skills.
to secondary generalised seizures in the majority of patients Although the EEG was not included in the diagnostic
(ILAE, 1981). The type of epilepsy in one patient whose criteria for epilepsy in our study, the high sensitivity
seizures consisted of sudden falls, in whom the EEG was (80°lo)and specificity (87°lo)rates of paroxysmal
normal,was unclassifiable (ILAE,1981). abnormalities suggests that the interictal EEG has a
useful role in assisting with the diagnosis of epilepsy.
This study has also demonstrated the importance
Discussion
of the EEG in assisting in the classification of seizure
This is the first reported prevalence study of epilepsy type. Nine (75%) of the 12 patients with paroxysmal
in Down's syndrome based on a community sample. abnormalities on EEG showed a temporal or parietal
The prevalence rate of Down's syndrome in the adult lobe focus, independent of age or dementia. This
population of 0.76 per 1000compares well with that contrasts with the findings of Tangye (1979), who
reported by Mallon ci a! (1991) and confirms the reported no localising features on EEG in 13 cases
reliability of the screening method. A number of of epilepsy. We have taken the EEG evidence to
factors suggest that the prevalence rate did approxi support a diagnosis of partial epilepsy in all 12 cases
mate to full ascertainment. First, Down's syndrome with EEG abnormalities. We have found no evidence
is easily recognised as a cause of mental handicap of primary generalised epilepsy in this series. Taken
and this has led to a high uptake of services, such together with the distribution of age of onset—allbut
as attendance at adult training centres. Second, the two with adult onset—thefindings from the present
Social Services Register was used to identify those study suggest that epilepsy in Down's syndrome is
few adults with Down's syndrome not attending of the partial type, with secondary generalisation.
adult training centres. Third, the pattern and The seizure frequency observed in our sample of
delivery of hospital servicesfor mentally handicapped adults with Down's syndrome is less than that
people in the Eastern Health and Social Services reported in the mentally handicapped population in
Board is such that persons with Down's syndrome general. Forsgren ci a!, in a study of the prevalence
from the Belfast catchment area who require of epilepsy in 299 mentally retarded children and
specialist hospital care would be admitted to adults in a large Swedish community, reported
Muckamore Abbey Hospital. The increased longevity that 32% had been seizure-free during the previous
in Down's syndrome is demonstrated in this study, year; 31°lohad had less than 1 seizure per month;
with a significant percentage (30%) of adults now and 27% had daily to weekly seizures (Forsgren
living beyond the age of 40. ci a!, 1990).
EPILEPSYIN ADULTSWITHDOWN'SSYNDROME 531

Fourteen of the 15 patients receiving anti-epileptic l0% prevalence of epilepsy in autopsy-proven


drugs were on monotherapy. In contrast to the Alzheimer's disease without Down's syndrome
community group, who were treated with carba (Hauser et a!, 1986).
mazepine in most cases, all seven hospital in-patients The fmdings provide evidence for two distinct aeti
on anti-epileptic drugs were receiving sodium ological processes for epilepsy in Down's syndrome.
valproate, known for its greater efficacy in absence Late-onset epilepsy is associated with neuronal
seizures. Given that the majority of our patients had degeneration consistent with Alzheimer's disease.
partial seizures, carbamazepine may be a more Early-onset epilepsy is related to another, as yet
effective first-line treatment (Mattson et a!, 1992). unknown, physiological abnormality associated with
The age distribution of onset of epilepsy showed the development of an epileptic focus. Further
an early peak in the third decade, with only one prospective longitudinal studies are required to
patient with an onset of epilepsy in the 30—44 age elucidate possible predictive factors in the develop
range. A second peak in the age of onset was ment of epilepsy, to establish the characteristics of
observed in the fifth and sixth decades. While these the early-onset and the late-onset groups, and to
figures suggest a bimodal distribution, the small clarify the relationship between late-onset epilepsy
sample size does not permit a firm conclusion to be and Alzheimer's disease.
drawn. In a recent study of seizure disorder in 405
people with Down's syndrome, age range 6 months Acknowledgements
to 45 years, Pueschel eta! (1991) found a clear peak
We areindebted
toDrsG.J.Calvert,
C.M.Marriott
andM.GA.
in age of onset of seizures between 20 and 30 years McGinnity for permission to study their patients. We would like
of age, which is consistent with our fmdings. The to thank the staff of the adulttrainingcentres,Belfast,the nursing
same authors also reported that few seizures staff at Muckamore Abbey Hospital and the staff of the Clinical
developed after the age of 1 year and before 19 years. Neurophysiology Unit, Department of Mental Health, Belfast City
Hospital, for their cooperation. We are grateful to Dr I. Bankhead,
The strongest evidence for the existence of two Department of Psychology, Muckamore Abbey Hospital, and
subgroups, however, emerges from both the EEG Dr C. Patterson, Department of Public Health, Queen's University,
fmdings and the coexistence, or absence, of develop Belfast, for advice on statistics. We are obliged to Mrs D. McFetridge
mental regression with epilepsy. Of the 18 patients for typingthe script.
with epilepsy, eight showed clinical evidence of
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5R. W. McVicker, MRCPsych, MRCGP, DRCOG, Consultant Psychiatrist; 0. E. P. Shanks, FRCPsych, MRCP,
DCH, Consultant Psychiatrist, Muckamore Abbey Hospital, 1 Abbey Road, Muckamore, Antrim
BT4J 4SH; R. J. McClelland, FRCPsych,MD, PhD, DIC, Professor of Mental Health, The Queen's University
of Belfast, The Whitla Medical Building, 97 Lisburn Road, Belfast BT9 7BL

*Correspondence

(First received November 1991, final revision May 1993, accepted June 1993)