BRIEF COMMUNICATIONS A N D CASE REPORTS

Startle Epilepsy
Complicating Down
Syndrome during
Adulthood
S. GimPnez-Roldan, MD, and M. Martin, M D

A woman with D o w n syndrome-a
trisomy 21
karyotype-developed severe startle epilepsy a n d
spontaneous seizures at the age of 20 years. T r i g g e r i n g
factors, seizure patterns, a n d ictal electroencephalograms were t h e same as i n startle epilepsy occurring i n
children w i t h cerebral palsy b u t differed i n that there
was n o clinical or radiological evidence of a focal brain
lesion in the vicinity of the motor supplementary cortex. A therapeutic trial w i t h clonazepam substantially
reduced t h e frequency of reflex-induced and spontaneous seizures.
Gimenez-Roldan S, Martin M: Startle epilepsy
complicating Down syndrome during adulthood.
Ann Neurol 7:78-80, 1980

Some patients with D o w n s y n d r o m e d e v e l o p a progressive brain disorder after reaching adulthood. Rep o r t e d patients have usually displayed progressive
dementia, s o m e t i m e s associated with any of a number of neurological abnormalities including tremor, incoordination, flexor posture, and increased
t e n d o n reflexes [12]. I t s e e m s possible that t h e full
range of neurological complications of D o w n synd r o m e d u r i n g a d u l t h o o d has n o t yet b e e n completely
recorded. For instance, various subtle abnormalities
w e r e e n c o u n t e r e d in a series of adults with D o w n
s y n d r o m e c o m p a r e d with y o u n g patients; these consisted of a g r e a t e r incidence of o b j e c t identification
difficulties, p a l m o m e n t a l a n d s n o u t reflexes [ 131,
epilepsy [ 141, a n d pyramidal tract signs [7].
We r e p o r t h e r e a w o m a n with classic trisomy 2 1
who at the age of 20 years developed s e v e r e startle
epilepsy, an unusual form of reflex epilepsy n o t previously described in this association.
A 20-year-old woman was admitted to the hospital with a
four-month history of severe seizure disorder. Severe
psychomotor retardation had become evident during her
early development, and a diagnosis of Down syndrome had
From the Department of Neurology, Ciudad Sanitaria Provincial,
Madrid, Spain.
Accepted for publication May 25, 1979.
Address reprint requests to Dr GimPnez-Roldin, Department of
Neurology, Ciudad Sanitaria Provincial, calle Doctor Esquerdo 46,
Madrid 30, Spain.

been established o n the basis of a typical physical appearance. She received special education for the mentally retarded until the age of 18 years; at that time a routine
psychometric test battery showed an I Q of 42.
During rhe first three months following their onset, the
seizures occurred in response to sensory stimuli. Thereafter, some spontaneous diurnal and nocturnal seizures of
identical appearance were intermixed with them. Most of
the seizure-evoking stimuli were acoustic, although unexpected visual and proprioceptive stimuli were also occasionally effective. Seizure-triggering stimuli were frequently of relatively minor intensity, and activities of daily
living caused numerous episodes. Dropping a teaspoon,
hearing the doorbell ring, or a bout of coughing from a
nearby person were typical precipitating examples. A slight
stumble against a fold in the carpet or an unexpected soft
braking of the automobile while travelling were examples
of nonacoustic startles that would induce a seizure. The
frequency of seizures increased to approximately twenty a
day despite attempts to control them with carbamazepine,
400 mg per day, sodium phenytoin, 200 mg per day, plus
phenobarbital 90 mg daily, and diazepam, 20 mg per day.
O n examination she exhibited the classic features of
Down syndrome (Fig 1A) and a severe degree of mental
retardation. Neurologically she had mild to moderate generalized muscle hypotonia and a mild increase of deep tendon reflexes with flexor plantar responses.
Easily evoked seizures were filmed and electroencephalographically recorded. Following an unexpected clapping of the hands, she responded with a sudden and sustained forward flexion of the trunk with both arms rigidly
semiflexed over the chest (Fig lB), remaining expressionless and unresponsive during the episode. Recovery occurred 10 to 15 seconds later with a brief cry, and confusion continued for a few more seconds. O n at least three
occasions a generalized tonic-clonic convulsion followed a
fit such as the one described.
Bilateral synchronous trains of frontal theta waves and
paroxysmal discharges of generalized cielta activity were
occasionally recorded at rest in the electroencephalogram.
During an acoustic motor seizure (Fig 2) an initial brief
discharge of spikes in both paracentral areas was immediately followed by low-voltage, diffuse, fast activity. This
episode lasted 3.3 seconds and coincided with tonic flexion
of the trunk and limbs. It was followed by diffuse recruiting
rhythmic activity at a frequency of 4 Hz per second with
maximal amplitude over both frontal leads lasting 2.5 seconds. Immediately thereafter, slow waves intermixed with
muscle artifact appeared, coinciding with the brief crying
spell, and were followed by rapid return to the basic background pattern.
Extensive laboratory investigations, including cerebrospinal fluid protein and cell content, were normal. An air
encephalogram and C T scan of the head performed 18
months later were also normal. Psychological testing
(WAIS) performed o n admission and at follow-up showed a
full-scale I Q of 48. Chromosome analysis demonstrated a
trisomy 2 1 (47, X Y ,
21) formula.
A trial of clonazepam versus placebo therapy was
undertaken. The number of spontaneous (diurnal and nocturnal) and reflex-induced seizures suffered during the

78 0364-5 134/80/010078-03$01.25 @ 1979 by S. GimCnez-Roldan

+

F i g 1 . (A) The patieids facial appearance, showiiig characteristicfeatures of Down sjridronie. (B) Patient at the onset of
a startle-induced seizure, appearirzg expressiorilesJ and with
foruurdjexion of h e head and trunk.

i'ig 2. Electroencephalogram during a seizure induced by a
.!udden,unexpected noise (arrow, left). A discharge of spikes is
1 ollowed by dzzuse fast activity and then by dqfuse recruiting
9 hythmic activity. A brief crying spell at the end of the seizure
arrow, right) is preceded by slow waves andsome nzuscle ari !facts.

Case Report: GimPnez-Roldin and Martin: Startle Epilepsy in Down Syndrome 79

hospitalization was recorded daily. A sodium phenytoin
dosage of 150 mg per day was maintained throughout the
trial. During the placebo period the mean frequency of
startle-induced seizures was 5.9 per day, while the spontaneous diurnal and nocturnal attacks were 6.9 and 8 . 1 ,
respectively. Placebo tablets were gradually replaced by
clonazepam, up to 4.5 mg per day, and maintained over a
35-day period. O n this regimen reflex seizures decreased to
a mean daily frequency of 1.3, a 7 7 . 1 % improvement, and
spontaneous diurnal and nocturnal seizures declined to a
mean frequency of 2.2 and 3.4, respectively. Increasing the
dosage of clonazepam t o 5 mg per day and sodium phenytoin to 2 10 mg during a 23-day period did not further decrease any type of seizure, and the patient became excessivelv somnolent.

lepsy is not a feature of Alzheimer disease 161, which,
although frequently observed in adults with Down
syndrome, does not explain the clinical disorder in
our patient. As suggested by electrophysiological [51
and morphological data [ 111, other changes known to
develop in Down syndrome during adulthood, such
as widespread abnormality of brain synapses, might
play a role.
Chromosome analysis was performed by D r San Romin of the
Department of Genetics, Fundacibn Jimknez Diaz, Madrid. Antonio Culebras, MD, kindly helped in translation of the manuscript.

References
Discussion
Startle epilepsy was fully described by Alajouanine
and Gastaut [ l ] in children and adolescents with cerebral palsy manifested by mild hemiparesis or, more
rarely, spastic diplegia. It is usually associated with
focal brain lesions secondary to obstetric or postnatal
brain damage, but cases related to cerebral angioma
[ I ] and Sturge-Weber syndrome 191 have been described. Experimental data 121 and EEG studies in
humans 131 have correlated the onset of seizures with
a discharging focus in the vicinity of the supplementary motor area of the cortex. A primary form of
startle epilepsy has also been suggested [ 4 ] .
This form of reflex epilepsy is usually resistant to
conventional anticonvulsants and has led to surgical
attempts to resect the involved cortex [ 3 ] . In this
context, the usefulness of clonazepam appears to be
of interest. A similar beneficial effect has been observed in 5 patients with cerebral palsy (unpublished
data) as well as in other forms of reflex epilepsy such
as photoconvulsive [ 101 and primary reading epilepsy
[81.
The disorder i n this woman with Down syndrome
fulfills the diagnostic criteria for startle epilepsy proposed by Alajouanine and Gastaut [ 11 with regard to
triggering factors, seizure pattern, and ictal EEG. She
differed in that lateralized motor phenomena were
not observed during the seizures and clinical and
radiological evidence of an underlying focal brain lesion were absent. Another difference was the relatively late age of onset compared with previously reported cases i n which onset occurred between the
ages of 1 month and 6 years.
Although this unusual form of reflex epilepsy
during early adulthood in a patient with Down syndrome is unlikely to be a coincidental occurrence,
there was no evidence in our patient during an 18month follow-up of progressive mental or neurological deterioration as judged by her neurological
status, psychometric testing, and CT scan. With the
exception of photoconvulsive seizures, reflex epi-

80 Annals of Neurology

Vol 7 No 1 January 1980

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