Reex Myoclonic Epilepsy of Infancy: Seizures Induced by
Tactile Stimulation
Emanuela Claudia Turco, MD1, Elena Pavlidis, MD2, Carlotta Facini, MD2, Carlotta Spagnoli, MD2, Anna Andreolli, MD2,
Rosalia Geraci, EEG Tech1, and Francesco Pisani, MD1,2
Myoclonic epilepsy with reflex seizures in infancy is an extremely rare condition, in which seizures are provoked
mainly by auditory or auditory-tactile stimuli. To increase the awareness of pediatricians regarding this underrecog-
nized condition, we describe a child with seizures provoked only by the tactile stimulation of specific areas of the
head and face. (J Pediatr 2016;173:250-3).
M
yoclonic epilepsy in infancy (MEI) was initially
described in 19811 and, even though several re-
ports appeared afterward, no triggering factors
were noted except photosensitivity in some subjects.2 A
variant with reflex seizures (reflex myoclonic epilepsy of in-
fancy [RMEI]) was reported and described as a separate
condition several years later.3 These conditions are both
classified as MEI.4 In the reflex variant, myoclonic seizures
may be provoked more frequently by auditory stimuli or by
the combination of both auditory and tactile stimuli. How-
ever, some cases with sensitivity to tactile-only stimulation
have also been reported in the literature.5-7 We describe a
child who exhibited RMEI with both spontaneous seizures
during drowsiness and sleep, and reflex seizures during
wakefulness and sleep. The reflex seizures were provoked
only by the tactile stimulation of the vertex of the head
and of the midline zones of the face, but there was no
response to auditory stimuli.
Case
A 15-month-old boy presented with a 3-month history of ep-
isodes of diffuse myoclonic jerks. These episodes were trig-
gered by the unexpected tactile stimulation of the vertex of
the head. Myoclonia were more evident in the eyelids,
neck, and upper limbs, causing loss of objects from the hands.
However, these movements sometimes also involved the
lower limbs, leading to the childs falling to the ground. He
was the only child of unrelated healthy parents. Family his-
tory was unremarkable. Psychomotor development had
been completely normal and no interruptions in the acquisi-
tion of developmental milestones or regression were
reported.
At the first evaluation, general and neurologic examina-
tions were normal. The Bayley Scale of Infant and Toddler
Development (Bayley-II) showed fully normal scores
(Mental Developmental Index = 93; Performance Devel-
EEG Electroencephalogram
MEI Myoclonic epilepsy in infancy
RMEI Reflex myoclonic epilepsy of infancy
250
opmental Index = 105). An ophthalmologic evaluation
including the fundus oculi was unremarkable as were
the electrocardiogram, echocardiogram, and abdominal
ultrasound scan. Blood screening, array comparative
genomic hybridization, and neurometabolic investiga-
tions (blood lactate and ammonia, plasma and urine
amino acids, urine organic acids, and serum acylcarnitine
profile) were normal. Brain magnetic resonance imaging
was normal.
Repeated polygraphic video-electroencephalograms
(EEGs) showed normal background activity with sporadic
interictal epileptic anomalies in the frontocentral regions.
Furthermore, generalized spike-wave and polyspike-wave
discharges with anterior predominance were recorded,
both spontaneously in drowsiness and sleep, as well as
with tactile stimulation in wakefulness and sleep
(Figures 1 and 2). Spontaneous generalized discharges
were not always accompanied by clinical manifestations.
The seizures could vary in intensity from time to time,
being mild (with only blinking or head nodding or
drop) or severe (with upward-outward movement of the
upper limbs and sudden projection or loss of objects
from the hands and, sometimes, flexion of the lower
limbs with falls to the ground; Video; available at www.
jpeds.com). The only type of tactile stimulation
provoking reflex myoclonic seizures was the sudden
tapping of the mouth, nose, glabella, and vertex of the
head. Both acoustic stimuli and tactile stimulation of
other parts of the body (eg, masseter muscles, hands, or
feet) were evaluated and resulted in no response. Only
one time during follow-up intermittent photic
stimulation evoked a photoparoxysmal response (type I
and III),8 without any clinical correlate.
Antiepileptic therapy with sodium valproate was pro-
posed, but not started because of parental refusal. Both reflex
From the 1Child Neuropsychiatry Unit, Mother and Child Department, University-
Hospital of Parma; and 2Child Neuropsychiatry Unit, Neuroscience Department,
University of Parma, Parma, Italy
The authors declare no conflicts of interest.
0022-3476/$ - see front matter. 2016 Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.jpeds.2016.03.001
 Volume 173  June 2016

Figure 1. Spontaneous generalized spike-wave and polyspike-wave discharges with anterior predominance both in A,
drowsiness and B, sleep. B, During sleep, the generalized discharges were accompanied by a burst of rhythmic myoclonias
recorded on the 2 deltoid muscles, the right sternocleidomastoid muscle and, with a minor intensity, on the 2 femoral quadriceps
muscles (bandpass filter, 1.6-30 Hz; notch, 50 Hz; sensitivity, 150 mV/cm). ECG, electrocardiogram; L Delt., left deltoid; L Fem.,
left femoral; R Delt., right deltoid; R Fem., right femoral; R Scm, sternocleidomastoid muscle.

and spontaneous seizures disappeared 6 months after their
onset. At the last follow-up visit, performed 1 year after the
onset of epilepsy, the EEG recording, in wakefulness and
sleep, confirmed the absence of seizures and showed normal
background activity, even with tapping of the mouth, nose,
glabella, and vertex of the head. Psychomotor development
was still completely normal for age.
Discussion
MEI is an idiopathic, generalized epilepsy, with a male pre-
dominance, characterized by spontaneous myoclonic sei-
zures presenting during the first 3 years of life in
neurologically and developmentally normal children.6 A
variant with reflex seizures was first described in 1995.3
There is a debate as to whether or not MEI and RMEI
are two separate conditions. RMEI seems to have an earlier
onset, a better response to antiepileptic drugs, and a better
cognitive outcome.9 However, RMEI is not currently
recognized as a distinct entity.4,6,10,11 In our patient, no
family history for febrile seizures or epilepsy was reported;
however, a complex genetic inheritance of RMEI has been
suggested, owing to the presence of febrile convulsions in
some patients and to a family history of febrile convulsions
or idiopathic generalized epilepsies in a significant per-
centage of cases.7,9 Even though the precise pathogenic
mechanism underlying this condition are unclear, an
age-dependent hyperexcitability of the motor cortex may
be involved.5,6,9 Although different types of provocative
stimuli are reported, including thermal, proprioceptive, vi-
sual, and photic triggers in various combination, the
acoustic and tactile stimuli seem to be the most provoca-
tive.3,10,12-15 As confirmed in our case, photosensitivity is
occasionally evident on EEG, but is not a specific feature
of this type of epilepsy6,9 and sometimes does not trigger
seizures. Expected or frequently repeated stimuli are not
able to provoke seizures.5,9 Although seizures with falls
are possible, as seen in our patient and in other reports,9
they are uncommon.6,10 We further confirm that sponta-
neous seizures in RMEI (32% of the subjects) usually oc-
curs after the onset of the reflex seizures and were
evident only during drowsiness and sleep.7,9
In the present case, even though there were spontaneous
seizures, epilepsy resolved without antiepileptic treatment
in 6 months. This finding suggests that, because RMEI is
a self-limited condition with a brief duration of seizures
and fast remission of epilepsy, it is possible, at least for pa-
tients suffering from reflex-only seizures, to avoid antiepi-
leptic therapy. Furthermore, another option would be to
postpone therapy in case seizures persist for >6 months
or if they become more frequent, longer, or sponta-
neous.3,9,13 The association of normal psychomotor devel-
opment and well-organized EEG background activity in a
child with only reflex myoclonic seizures or both reflex
and spontaneous ones would suggest a reflex variant of
MEI. This is a rare and probably underestimated condition,
251
THE JOURNAL OF PEDIATRICS  www.jpeds.com Volume 173

Figure 2. Reflex myoclonic seizure provoked by tactile stimulation (arrow) during wakefulness and related to clear generalized
ictal discharges at the EEG and rhythmic myoclonic jerks on the different recorded muscles (bandpass filter, 1.6-30 Hz; notch,
50 Hz; sensitivity, 150 mV/cm).

which could be easily misinterpreted as an excessive startle
reaction owing to the short duration of the events.5,9 The
acknowledgment of these clinical phenomena as possible
seizures is important for clinicians to establish a proper dif-
ferential diagnosis, allowing the postponement of second-
line diagnostic workup. Indeed, several other conditions
may exhibit myoclonic jerks, and these can be either
epileptic or nonepileptic with an excessive startle response,
sometimes owing to chromosomal abnormalities or severe
neurometabolic disorders (Table I; available at www.
jpeds.com).5,9,16-22 It is important for pediatricians to
recognize these movements as potential seizures and to
perform a thorough medical, developmental, and family
history as well as a thorough neurologic examination as
252
the first step. It is particularly important for pediatricians
to recognize and offer reassurance for common, benign
conditions, like benign myoclonus of early infancy and
benign neonatal sleep myoclonus. EEG plays a central role
in cases for whom seizures are causes for concern,
clarifying between epileptic and nonepileptic myoclonus.
The results of the EEG and the childs developmental
history will help to dictate the necessity and extent of
additional second-line investigations (Table II; available at
www.jpeds.com). In the present condition, unremarkable
neuroimaging findings and metabolic assessment further
confirm the diagnosis.
Clinicians should be alerted to the existence of RMEI and
its clinical features. Indeed, a proper clinical identification is
Turco et al
June 2016
important to address the appropriate diagnostic workup and
therapeutic measures, and to provide parents with prognostic
information. n
Submitted for publication Oct 22, 2015; last revision received Jan 20, 2016;
accepted Mar 1, 2016.
Reprint requests: Elena Pavlidis, MD, Child Neuropsychiatry Unit, Mother and
Child Department, University-Hospital of Parma, Via Gramsci 14, 43126 Parma
(PR), Italy. E-mail: elena.pavlidis2@gmail.com
References
1. Dravet C, Bureau M. The benign myoclonic epilepsy of infancy (authors
transl). Rev Electroencephalogr Neurophysiol Clin 1981;11:438-44.
2. Dravet C, Bureau M, Genton P. Benign myoclonic epilepsy of in-
fancy: electroclinical symptomatology and differential diagnosis
from the other types of generalized epilepsy of infancy. Epilepsy
Res Suppl 1992;6:131-5.
3. Ricci S, Cusmai R, Fusco L, Vigevano F. Reflex myoclonic epilepsy in in-
fancy: a new age-dependent idiopathic epileptic syndrome related to
startle reaction. Epilepsia 1995;36:342-8.
4. Berg AT, Berkovic SF, Brodie MJ, Buchhalter J, Cross JH, van Emde
Boas W, et al. Revised terminology and concepts for organization of sei-
zures and epilepsies: report of the ILAE Commission on Classification
and Terminology, 2005-2009. Epilepsia 2010;51:676-85.
5. Kurian MA, King MD. An unusual case of benign reflex myoclonic
epilepsy of infancy. Neuropediatrics 2003;34:152-5.
6. Darra F, Fiorini E, Zoccante L, Mastella L, Torniero C, Cortese S, et al.
Benign myoclonic epilepsy in infancy (BMEI): a longitudinal electroclin-
ical study of 22 cases. Epilepsia 2006;47 Suppl 5:31-5.
7. Verrotti A, Matricardi S, Capovilla G, DEgidio C, Cusmai R, Romeo A,
et al. Reflex myoclonic epilepsy in infancy: a multicenter clinical study.
Epilepsy Res 2013;103:237-44.
8. Waltz S, Christen HJ, Doose H. The different patterns of the photopar-
oxysmal responsea genetic study. Electroencephalogr Clin Neurophy-
siol 1992;83:138-45.
9. Verrotti A, Matricardi S, Pavone P, Marino R, Curatolo P. Reflex
myoclonic epilepsy in infancy: a critical review. Epileptic Disord 2013;
15:114-22.
Reflex Myoclonic Epilepsy of Infancy: Seizures Induced by Tactile Stimulation
CLINICAL AND LABORATORY OBSERVATIONS
10. Auvin S, Pandit F, De Bellecize J, Badinand N, Isnard H, Motte J, et al.
Benign myoclonic epilepsy in infants: electroclinical features and long-
term follow-up of 34 patients. Epilepsia 2006;47:387-93.
11. Guerrini R, Mari F, Dravet C. Idiopathic myoclonic epilepsies in infancy
and early childhood. In: Bureau M, Genton P, Dravet C, Delgado-
Escueta A, Tassinari CA, Thomas P, et al. eds. Epileptic syndromes
in infancy, childhood and adolescence. 5th ed. London: John Libbey
Eurotext Ltd; 2012. p. 157-73.
12. Cuvellier JC, Lamblin MD, Cuisset JM, Vallee L, Nuyts JP. Lepilepsie
myoclonique benigne reflexe du nourrisson. Arch Pediatr 1997;4:755-8.
13. Deonna T. Reflex seizures with somatosensory precipitation. Clinical
and electroencephalographic patterns and differential diagnosis, with
emphasis on reflex myoclonic epilepsy of infancy. In: Zifkin BG,
Andermann F, Beaumanoir A, Rowan AJ, eds. Reflex epilepsies and re-
flex seizures: advances in neurology. Philadelphia: Lippincott-Raven
Publishers; 1998. p. 193-206.
14. Zafeiriou D, Vargiami E, Kontopoulos E. Reflex myoclonic epilepsy in
infancy: a benign age-dependent idiopathic startle epilepsy. Epileptic
Disord 2003;5:121-2.
15. Capovilla G, Beccaria F, Gambardella A, Montagnini A, Avantaggiato P,
Serri S. Photosensitive benign myoclonic epilepsy in infancy. Epilepsia
2007;48:96-100.
16. Guerrini R, Genton P, Bureau M, Dravet C, Roger J. Reflex seizures are
frequent in patients with Down Syndrome and epilepsy. Epilepsia 1990;
31:406-17.
17. Yang Z, Liu X, Qin J, Zhang Y, Bao X, Wang S, et al. Clinical and elec-
trophysiological characteristics of startle epilepsy in childhood. Clin
Neurophysiol 2010;121:658-64.
18. Bakker MJ, van Dijk JG, van den Maagdenberg AMJM, Tijssen MAJ.
Startle syndrome. Lancet Neurol 2006;5:513-24.
19. Meinck HM. Startle and its disorders. Neurophysiol Clin 2006;36:
357-64.
20. Caraballo RH, Capovilla G, Vigevano F, Beccaria F, Specchio N,
Fejerman N. The spectrum of benign myoclonus of early infancy:
clinical and neurophysiologic features in 102 patients. Epilepsia
2009;50:1176-83.
21. Ferlazzo E, Adjien CK, Guerrini R, Calarese T, Crespel A, Elia M, et al.
Lennox-Gastaut syndrome with late-onset and prominent reflex seizures
in trisomy 21 patients. Epilepsia 2009;50:1587-95.
22. Maurer VO, Rizzi M, Bianchetti MG, Ramelli GP. Benign neonatal sleep
myoclonus: a review of the literature. Pediatrics 2010;125:e919-24.
253
253.e1

THE JOURNAL OF PEDIATRICS

Table I. Differential diagnosis of myoclonus in infancy
EEG
background
Clinical Presence of Presence of activity and
conditions Psychomotor reflex non-myoclonic interictal
with myoclonic Age at development myoclonic epileptic epileptic Epileptic Neuroimaging Metabolic Known genetic
manifestations onset at onset phenomena seizures discharges discharges abnormalities alterations abnormalities Outcome
MEI 4 mo-3 y Normal. Myoclonic seizures (Rare simple Normal; possible + (Generalized fast Not reported. Commonly favorable.
triggered by febrile seizures.) interictal spike-waves or
stimuli, in abnormalities. polyspike-waves.)
particular sudden
noise or touch
(reflex MEI).
Dravet 5-8 mo Normal. They can be initiated + Usually normal at the + (Generalized /+ SCN1A gene Unfavorable
syndrome by photic onset; then normal spike-waves or mutations in (persistent
stimulation, or slow and poorly multiple spike- 70%-80% of seizures, cognitive


variation in light organized; waves, at 3 Hz or patients; impairment, motor

www.jpeds.com
intensity, closure interictal more, with higher GABRG2, disability,
of the eyes and abnormalities and voltage in SCN1B, mortality for
fixation of possible frontocentral PCDH19 gene status epilepticus,
patterns. photosensitivity. areas and vertex; mutations are sudden
generalized uncommon unexpected death,
discharges, when (PCDH19 drowning,
present, are mutations in accident,
associated with females with infection).
focal and Dravet
multifocal syndrome-like
discharges.) phenotype).
Epilepsy with 7 mo-6 y Normal. Some patients are + Normal at onset; + (Bursts of spike/ Usually . SCN1A and Variable (from
myoclonic photosensitive. typical patterns polyspike and SLC2A1 gene seizures
atonic are described. wave complexes mutations are resolution to
(previously at 2-4 Hz.) rarely found. intractable
astatic) epilepsy; from
seizures normal cognitive
outcome to severe
mental
retardation; cases
of mild behavioral
problems).
West 3-9 mo Variable, usually Not reported. Epileptic spasms can Hypsarrhythmia. + (Various patterns. Several +/ Many gene Mostly unfavorable.
syndrome delayed. be associated with The most common abnormalities mutations and
a partial seizure. characterized by depending on chromosomal
diffuse high etiology. abnormalities,
amplitude slow depending on
waves, with etiology.
possible
predominance
over one
hemisphere,

Volume 173
variably
Turco et al

associated with a
brief beta activity.)
(Continued )
Reflex Myoclonic Epilepsy of Infancy: Seizures Induced by Tactile Stimulation

June 2016
Table I. Continued
EEG
background
Clinical Presence of Presence of activity and
conditions Psychomotor reflex non-myoclonic interictal
with myoclonic Age at development myoclonic epileptic epileptic Epileptic Neuroimaging Metabolic Known genetic
manifestations onset at onset phenomena seizures discharges discharges abnormalities alterations abnormalities Outcome
Lennox-Gastatut <8 y Variable: normal Rarely reported + Varies with age and + (Myoclonic-atonic /+ +/ Many gene Usually unfavorable
syndrome or delayed. (ie, described etiology. seizures are mutations and (persistence of
in trisomy 21 Mostly abnormal. associated with chromosomal seizures,
patients). generalized abnormalities, progressive
discharges of slow depending on mental
spike-waves or etiology. deterioration).
polyspike-waves;
myoclonia with
bilateral
symmetric spike-
waves preceding
$1 slow waves.)
Progressive Variable, Various Usually spontaneous + Initially possible + Variable Various All genetically The severity and the
myoclonus during the associations myoclonus normal depending metabolic inherited with progression of the
epilepsies with first years of psychomotor (photosensitivity background with on etiology. alterations an autosomal neurologic
early onset of life. impairment has been generalized or can be recessive deterioration vary
(eg, ceroid- and neurologic described in some multifocal spikes. detected, fashion, with considerably from
lipofuscinosis, signs may be forms). Deterioration of guiding to a few exceptions one etiology to
MERRF) present. background specific (eg, maternal another.
activity over time. etiology. inheritance in
MERRF).
Startle Wide range Variable, Myoclonic seizures + Normal or abnormal. + (Diffuse +/ +/ Depending on Poor (drug refractory
epilepsy of ages. cognitive triggered by Frequent interictal attenuation of etiology. seizures,

CLINICAL AND LABORATORY OBSERVATIONS

It may start abnormalities sudden and EEG background secondarily
in childhood. are described. unexpected abnormalities. activity, cognitive
auditory, sometimes impairment).
somatosensory or followed by low-
visual stimuli. voltage fast
activity or
generalized spike
and waves,
polyspike and
waves, or slow
waves.)
Hyperekplexia Variable Normal. Excessive startling to Not reported. Usually normal. Not reported. GLRA1, GLRB, Excessive jerking to
(from an unexpected GPHN, external
neonatal stimulus, ARHGEF9 stimulation
period to particularly gene persists. Mild
childhood auditory. mutations. delay, gait
and puberty). disturbance and
uncontrolled falls
are reported.
Newborns are at risk
for sudden infant
death.
253.e2

(Continued )
253.e3

THE JOURNAL OF PEDIATRICS

Table I. Continued
EEG
background
Clinical Presence of Presence of activity and
conditions Psychomotor reflex non-myoclonic interictal
with myoclonic Age at development myoclonic epileptic epileptic Epileptic Neuroimaging Metabolic Known genetic
manifestations onset at onset phenomena seizures discharges discharges abnormalities alterations abnormalities Outcome
Benign 1-12 mo Normal. Not reported. Not reported. Normal. Not reported. Not reported. Usually favorable
myoclonus (disappearance of
of early episodes between
infancy 6 and 30 mo).
Benign 1 mo Normal. Myoclonus occurs Normal. Usually . Not reported. Usually favorable
neonatal only during sleep (disappearance of
sleep and stops with episodes by the
myoclonus arousal. It may be age of #12 mo in
induced by 97% of cases).


rocking the infant

www.jpeds.com
or by repetitive
sounds and it may
be worsened by
holding the limbs
or on medication
with antiepileptic
drugs.

, negative; +, positive; +/ , possible; MERRF, myoclonic epilepsy with ragged red fibers.
Background activity: Any EEG activity representing the setting in which a given normal or abnormal pattern appears and from which such pattern is distinguished. (International Federation of Societies for Clinical Neurophysiology. Recommendations for the practice of
clinical neurophysiology: guidelines of the International Federation of Clinical Neurophysiology. Electroencephalogr Clin Neurophysiol Suppl 1999;52:1-304).
Interictal Epileptic discharges: a subcategory of epileptiform pattern, in turn defined as distinctive waves or complexes, distinguished from background activity, and resembling those recorded in a proportion of human subjects suffering from epileptic disorders..
(International Federation of Societies for Clinical Neurophysiology. A glossary of terms most commonly used by clinical electroencephalographers. Electroencephalogr Clin Neurophysiol 1974;37:538-48).

Volume 173
Turco et al
June 2016 CLINICAL AND LABORATORY OBSERVATIONS

Table II. Diagnostic workup for myoclonus of infancy

First-line investigations
History for familial and personal antecedents.
General and neurologic examinations.
Prolonged polygraphic video-EEG
 During wakefulness and sleep;
 Polygraphic recordings: EEG, electrocardiogram, surface EMG
(neck muscles, deltoid and femoral);
 Stimulation test: tapping test (of peculiar parts of the body)
and proprioceptive, acoustic, and photic stimulation; and
 Jerk-locked back averaging (to disclose cortical spikes not evident with
the conventional EEG-EMG recording).
Neuropsychological evaluation, including cognitive and behavioral
assessment.
Second-line investigations
Brain magnetic resonance imaging.
Blood screening and neurometabolic investigations (blood lactate and
ammonia, plasma and urine amino acids, urine organic acids, and serum
acylcarnitine profile).
Genetic assessment: karyotype, array comparative genomic hybridization
(other investigations based on clinical suspect).
Others investigations: ophthalmologic evaluation with assessment of
fundus oculi, electrocardiogram, echocardiogram, and abdominal
ultrasound.

EMG, electromyogram.

Reflex Myoclonic Epilepsy of Infancy: Seizures Induced by Tactile Stimulation 253.e4