ARTICLE IN PRESS+ModelEPIRES-4793; No. of Pages 8

Epilepsy Research (2012) xxx, xxx—xxx

jou rn al h om epa ge: www.elsev ier .com/ locate /ep i lepsyres

Reflex myoclonic epilepsy in infancy: A multicenterclinical study

Alberto Verrotti a, Sara Matricardia,∗, Giuseppe Capovillab,Claudia D’Egidioa, Raffaella Cusmaic, Antonino Romeod, Dario Prunae,Piero Pavonef, Silvia Cappanerag, Tiziana Granatah, Giuseppe Gobbi i,Pasquale Strianoj, Salvatore Grossok, Pasquale Parisi l, Emilio Franzonim,Salvatore Strianon, Alberto Spaliceo, Raffaella Marinoa, Federico Vigevanoc,Giangennaro Coppolap

a Department of Pediatrics, University of Chieti, Chieti, Italyb Epilepsy Center, Department of Child Neuropsychiatry, ‘‘C. Poma Hospital’’, Mantova, Italyc Division of Neurology, Neurology Unit, ‘‘Bambino Gesù’’ Children’s Hospital, IRCCS, Rome, Italyd Epilepsy Center, Department of Child Neuropsychiatry and Neurophysiology, ‘‘Fatebenefratelli e Oftalmico’’ Hospital, Milan,Italye Division of Child Neurology and Psychiatry, Azienda Ospedaliero Universitaria of Cagliari, Cagliari, Italyf Department of Pediatrics and Pediatric Emergency ‘‘Costanza Gravina’’ University Hospital ‘‘Vittorio Emanuele Policlinico’’ ofCatania, Catania, Italyg Department of Pediatric Neurology, Ospedali Riuniti of Ancona, Ancona, Italyh Department of Paediatric Neuroscience, IRCCS Foundation Neurological Institute C. Besta, Milan, Italyi Child Neurology and Psychiatry Unit, Neuroscience Department, ‘‘Maggiore’’ Hospital of Bologna, Bologna, Italyj Muscular and Neurodegenerative Disease Unit, ‘‘G. Gaslini’’ Institute, University of Genova, Genova, Italyk Department of Pediatrics, Pediatric Neurology Unit, University of Siena, Siena, Italyl Chair Pediatrics, II Faculty of Medicine, ‘‘La Sapienza’’ University of Rome, Rome, Italym Child Neurology and Psychiatry Unit, University of Bologna, ‘‘S. Orsola-Malpighi’’ Hospital, Bologna, Italyn Epilepsy Center, Division of Child Neurology, ‘‘Federico II’’ University of Napoli, Napoli, Italy

Please cite this article in press as: Verrotti, A., et al., Reflex myoclonic epilepsy in infancy: A multicenter clinical study.Epilepsy Res. (2012), http://dx.doi.org/10.1016/j.eplepsyres.2012.07.004

o Department of Pediatrics, ‘‘La Sapienza’’ University of Rome, Rome, Italyp Clinic of Child and Adolescent Neuropsychiatry, Medical School, University of Salerno, Salerno, Italy

Received 4 March 2012; received in revised form 26 June 2012; accepted 3 July 2012

∗ Corresponding author at: Department of Pediatrics, University of Chieti, Via dei Vestini 5, 66100 Chieti, Italy. Tel.: +39 871358690;fax: +39 871 574831.

E-mail addresses: averrott@unich.it (A. Verrotti), sara.matricardi@yahoo.it (S. Matricardi), pippo.capovilla@aopoma.it (G. Capovilla),claudia.degidio@hotmail.it (C. D’Egidio), cusmai@opbg.net (R. Cusmai), antonino.romeo@fbf.milano.it (A. Romeo),d.pruna@tiscali.it (D. Pruna), ppavone@unict.it (P. Pavone), silvia.cappanera@gmail.com (S. Cappanera),Tiziana.Granata@istituto-besta.it (T. Granata), giuseppe.gobbi@ausl.bologna.it (G. Gobbi), pstriano@email.it (P. Striano),grosso@unisi.it (S. Grosso), pasquale.parisi@uniroma1.it (P. Parisi), emilio.franzoni@unibo.it (E. Franzoni), sstriano@libero.it (S. Striano),childneurology.sapienzaroma@live.it (A. Spalice), raffocchia@yahoo.it (R. Marino), federico.vigevano@opbg.net (F. Vigevano),gcoppola@unisa.it (G. Coppola).

0920-1211/$ — see front matter © 2012 Published by Elsevier B.V.http://dx.doi.org/10.1016/j.eplepsyres.2012.07.004

ARTICLE IN PRESS+ModelEPIRES-4793; No. of Pages 8

2 A. Verrotti et al.

Summary:Purpose: To describe the clinical and electroencephalographic (EEG) features of reflex myoclonicepilepsy in infancy (RMEI) and long-term cognitive outcome.Methods: We enrolled 31 children from 16 neuropediatric centres in Italy, who underwent clinicaland video-EEG evaluation. Cognitive assessment was performed in all patients using standardizedpsychometric tests.Results: The age at onset ranged from 3 to 24 months of age. Seizures were characterisedin all patients by symmetric myoclonic seizures (MS), triggered by sudden unexpected acoustic(38.7%) or tactile stimuli (29%) or both (29%). Spontaneous attacks were reported in 32.2% ofthe cases. Ictal EEG showed generalized high-amplitude 3 Hz polyspike and wave discharges,synchronous with brief rhythmic bursts of electromyographic activity. Patients were re-evaluatedafter a period of 7.2 ± 5.6 years. The prognosis for seizure control was excellent in all cases andreflex MS disappeared spontaneously or after valproate treatment. The cognitive outcome wasexcellent in 90.3% of children.Conclusions: RMEI appears to be a variety of idiopathic generalized epilepsy with specific features

lly no

KEYWORDSReflex myoclonic epilepsyin infancy;Long-term cognitiveoutcome;Acoustic and/or tactilestimuli;Valproate treatment;Idiopathic generalizedepilepsy

B.V.

I

Btt1gsontiC

MpeeaC1KgoiMsR

bpc

anr

M

Pm

tutnigw

(ana(i

e

fi(

iistoaaslniss

aCtest for children aged 6.0—16.11 years (Wechsler, 1991).

Wechsler Adult Intelligence Scale — Third edition (WAIS

that occurs in developmenta© 2012 Published by Elsevier

ntroduction

enign myoclonic epilepsy in infancy (BMEI) is charac-erized by the occurrence of myoclonic seizures (MS) inhe first 3 years of life in normal infants (Dravet et al.,985, 1992). It has been classified among the idiopathiceneralized epilepsies (IGE) in the 1989 International Clas-ification (Commission on Classification and Terminologyf the International League Against Epilepsy, 1989); andow included as Myoclonic epilepsy in infancy (MEI) amonghe electroclinical syndromes arranged by age at onset innfancy, in the recent report of the ILAE Commission onlassification and Terminology (Berg et al., 2010).

Recently, some authors have described cases with ‘‘reflexS’’, triggered by unexpected noise or touch and haveroposed to name this clinical entity: ‘‘reflex myoclonicpilepsy in infancy-RMEI’’ (Ricci et al., 1995). RMEI isxtremely rare and, to the best of our knowledge, therere 25 cases published in the literature (Ricci et al., 1995;uvellier et al., 1997; Giovanardi Rossi et al., 1997; Deonna,998; Fernandez-Lorente et al., 1999; Zafeiriou et al., 2003;urian and King, 2003; Caraballo et al., 2003), all showedeneralized reflex myoclonic jerks starting in the first 2 yearsf life. RMEI merits greater interest because it shows clin-cal and electroencephalographic (EEG) features similar toEI, but differentiated by the presence of reflex MS. Other

eizures (e.g. atonic and/or tonic seizures) are not part ofMEI.

RMEI may be underdescribed and underevaluatedecause the short duration of the event, possibly misinter-reted as ‘‘excessive startle reaction’’ in otherwise healthyhildren.

Data on long-term follow-up are still limited.To gain further insights into the clinical and EEG char-

cteristics of this syndrome and to evaluate the long-termeurodevelopmental outcome, a multicenter study is car-ied out by collecting data of children with RMEI.

Please cite this article in press as: Verrotti, A., et al., Reflex mEpilepsy Res. (2012), http://dx.doi.org/10.1016/j.eplepsyres.

ethods

atients were recruited from 16 Pediatric Neurology Depart-ent in Italy.

Ia

a

rmal children.

All children had diagnosis based upon the following cri-eria: (1) symmetric myoclonic jerks, triggered by suddennexpected tactile or acoustic stimuli; (2) onset of MS inhe first 2 years of life; (3) normal pregnancies and peri-atal history; (4) normal neuroradiological and metabolicnvestigations; (5) MS associated with an EEG discharge ofeneralized high-amplitude spike-wave (SW) or polyspike-ave (PSW) at 3 Hz on normal background activity.

The exclusion criteria were: (1) other seizures typespartial, tonic, tonic-clonic, atonic, asymmetric myoclonias,typical absences); (2) abnormal pre-, peri- and post-atal history; (3) pathological neurological examination; (4)bnormal psychomotor development (delay or regression);5) pathological findings on neuroradiological and metabolicnvestigations.

For each patient, personal and family histories ofpilepsy or febrile seizures were documented.

The children were evaluated periodically and thenal evaluation was performed after 7.2 ± 5.6 yearsmean ± standard deviation) from the onset.

Developmental and cognitive assessment was performedn all patients using standardized psychometric tests accord-ng to their age. In particular, Griffith’s mental developmentcales (GMDS) were performed to measure developmentrends which are significant for intelligence, or indicativef functional mental growth from birth to a developmentalge of eight years. There are two sets of scales, one for eachge group, 0—2 years and 2—8 years. Within the 0—2 yearcales, a profile is obtained from five subscales examiningocomotor, personal-social, language, eye-and-hand coordi-ation and performance. In the 2—8 year scales, this profiles expanded to add a practical reasoning subscale. Thesecales provide a general developmental quotient (GDQ) andeparate subquotients (DQs) for each area of development.

In 6 years old children and older, cognitive functions werenalysed by means of the Wechsler Intelligence Scale forhildren — Third edition (WISC III): standardized intelligence

yoclonic epilepsy in infancy: A multicenter clinical study.2012.07.004

II) is designed to assess cognitive functions in adolescentsnd young adults older than 17 years (Wechsler, 1997).

All children underwent periodical clinical evaluationnd repeated video-EEG and polygraphic recording during

IN+Model

jc(

iw

T

Awwas0j

c(coar

omwidI

bf(t

D

Rer

p

eFKtfic

FoteL

ARTICLEEPIRES-4793; No. of Pages 8

Reflex myoclonic epilepsy in infancy

wakefulness and sleep. The patients also underwent sen-sory stimulation with multiple unexpected acoustic stimuli(loud and soft noises), unexpected tactile (sudden touch indifferent part of the body) and thermal stimuli (cool water),visual stimuli (intermittent light stimulation — ILS).

Finally, we have subdivided our patients into two groups:patients treated with valproic acid (VPA), and untreatedpatients, to compare their clinical features.

Study was approved by the Ethical Committee of the Uni-versity of Chieti, Italy and informed consent was obtainedfrom the parents or legal guardians of all patients.

Statistical analysis was obtained using Student unpairedt-test or Fisher’s exact test. A p-value < 0.05 was consideredto be significant.

Results

At the onset

Thirty-one patients (male: female = 18: 13) were evaluated.The age at onset of reflex MS ranged between 3 and 24months (mean 11 months).

Clinical and EEG details of the patients are summarizedin Table 1.

A family history of febrile and/or afebrile seizures waspresent in 14 cases (45.1%), in first- or second-degreerelatives. Personal history of febrile convulsions (FC) wasreported in 3 patients (9.6%).

Ictal symptomatology of RMEI included generalizedmyoclonic jerks, involving the axis of the body and the limbs,provoking in some cases a head drop and an upward-outwardmovement of the upper limbs, with flexion of the lowerlimbs; considering the brief duration of the seizures and theyoung age of the patients, it was difficult to assess the levelof consciousness, which, when seizures occurred in cluster,appeared to be impaired. They were triggered by a sud-den noise and/or a sudden touch; surprise appeared to befundamental in triggering attacks. The threshold for attacksvaried according to the ambient noise level, attention leveland somnolence. Acoustic stimuli triggered MS in 12 subjects(38.7%): 8 children reacted only in response to loud noise,while the other 4 reacted also to soft noise. Tactile stimuliprovoked attacks in 9 children (29%): in the majority of them(6 children) sudden touch of the face or the head provokedattacks, whereas 2 children reacted more often to tactilestimuli of the face and upper limbs, only 1 patients showedcombined touch of face, upper and lower limbs. In 9 patients(29%) myoclonic jerks were triggered by both tactile andacoustic stimuli; MS were triggered by thermal stimulus (coolwater on face) and also acoustic stimuli only in one case.Visual stimulus, represented by ILS, did not trigger seizuresin these cases. The total number of attacks in each childvaried from day to day, depending mostly on the environ-mental precipitants. Spontaneous attacks were reported in10 cases (32.2%) and, generally, appeared months after thereflex attacks and were facilitated by sleep and somnolence.

Interictal EEG was normal in all cases, except for two,

Please cite this article in press as: Verrotti, A., et al., Reflex mEpilepsy Res. (2012), http://dx.doi.org/10.1016/j.eplepsyres.2

that showed bursts of generalized PSW and centro-temporalSW activity, occurring spontaneously. Sleep EEG was char-acterized in 11 cases (35.4%) by rare, generalized irregularPSW discharges, usually accompanied by brief and irregular

2

pt

PRESS3

erks. Ictal EEG manifestations consisted mainly of dis-harges of generalized high-amplitude SW or PSW at 3 HzFig. 1).

All patients showed normal cerebral magnetic resonancemaging (MRI) (except in two children in which cerebral MRIas not available) and metabolic investigations.

he end of follow-up

ll patients became seizure free and the EEG normalizedith the disappearance of seizures. No other types of seizureere observed in these children, particularly no atypicalbsences, tonic or atonic seizures. As a whole, the patientshowed a mean seizures duration of 7.8 months (range:.5—36). In 7 untreated children (22.5%), the myoclonicerks disappeared spontaneously.

Valproic acid (VPA) represented the drug of firsthoice and administered in monotherapy at low dosage20—25 mg/kg/day); it stopped the attacks in all treatedases (23 patients: 74.1%) after few months from the onsetf therapy. Only one patient received clonazepam (CZP) indd-on to VPA, with rapid seizures control. No patients expe-ienced adverse events during treatment.

Cognitive and behavioral evolution showed an excellentutcome with regular achievement of all developmentalilestones in 90.3% of children. Developmental assessmentas appropriate for age in 28 children, showing a GDQ or TIQ

n the normal range 80—120. Only 3 children showed a minorelay in language abilities, (one of these had a borderlineQ).

Statistical analysis (see Table 2) showed no differenceetween patients treated with VPA and untreated patients inamily and personal history of FC, family history of epilepsyns), and intellectual function (ns), except for a major dura-ion of RMEI in untreated patients (p < 0.05).

iscussion

MEI is a rare clinical entity and most of the availablevidences, based on anecdoctal cases, are inconclusiveegarding its evolution and prognosis.

In this study we clarify clinical and EEG findings witharticular attention to cognitive outcome.

According to previous reports (Ricci et al., 1995; Cuvelliert al., 1997; Giovanardi Rossi et al., 1997; Deonna, 1998;ernandez-Lorente et al., 1999; Zafeiriou et al., 2003;urian and King, 2003; Caraballo et al., 2003), in our patientshe onset of generalized reflex myoclonic jerks was in therst two years of life, with a short duration also in untreatedhildren.

Sex prevalence turned out that boys outnumber girls.Significant percentage of family history for IGE and/or

C in first- or second-degree relatives, and the occurrencef FC in some patients, suggested a complex genetic inheri-ance, as previously mentioned (Ricci et al., 1995; Cuvelliert al., 1997; Giovanardi Rossi et al., 1997; Fernandez-orente et al., 1999; Kurian and King, 2003; Caraballo et al.,

yoclonic epilepsy in infancy: A multicenter clinical study.012.07.004

003).All children were born to healthy parents after normal

regnancies and deliveries and all showed normal findingso neurological examinations.

Please cite

this article

in press

as: Verrotti,

A., et

al., Refl

ex m

yoclonic epilepsy

in infancy:

A m

ulticenter clinical

study.Epilepsy

Res. (2012),

http://dx.doi.org/10.1016/j.eplepsyres.2012.07.004

AR

TIC

LE

IN P

RE

SS

+Model

EPIRES-4793;

No.

of Pages

8

4

A. Verrotti

et al.

Table 1 Clinical and EEG details of the patients.

Patient Sex Familyhistory

Personalhistory

Age atonset(months)

Triggerstimuli

Clinicalcharacteristics

Spontaneousjerks

Otherseizures

InterictalEEG

Therapy Psychomotordevelopment

1 M FC (I and II) Normal 15 AcousticandTactile

generalizedmyoclonic jerks

Yes None wakefulness: normal;sleep: generalized PSWdischarges

none Normal

2 M FC (I and II) Normal 19 Acoustic generalizedmyoclonic jerks

Yes None wakefulness: normal;sleep: generalized PSWdischarges

VPA Normal

3 M FC (I), IGE(II)

Normal 24 Acoustic generalizedmyoclonic jerks

Yes None wakefulness: normal;sleep: generalized PSWdischarges

VPA Normal

4 F FC (I and II) Normal 13 Acoustic generalizedmyoclonic jerks

No None wakefulness: normal;sleep: generalized PSWdischarges

VPA Borderline IQand Languagedelay

5 M — — 11 Acoustic generalizedmyoclonic jerks

Yes None normal in wakefulnessand sleep

VPA Language delay

6 M FC FC 9 Acoustic generalizedmyoclonic jerks

No FC wakefulness: normal;sleep: generalized PSWdischarges

none Normal

7 F — FC 12 Acoustic generalizedmyoclonic jerks

No FC normal in wakefulnessand sleep

none Normal

8 M FC (I and II) — 8 AcousticandTactile

generalizedmyoclonic jerks

No None wakefulness: normal;sleep: generalized PSWdischarges

none Normal

9 F GTCS (I),JME (II)

— 6 AcousticandTactile

generalizedmyoclonic jerks

Yes None wakefulness: normal;sleep: generalized PSWdischarges

VPA e CZP Normal

10 M None Normal 22 Tactile generalizedmyoclonic jerks

No None wakefulness: isolatedcentro-temporal SW

VPA Normal

11 M None Normal 12 Acoustic generalizedmyoclonic jerks

No None wakefulness: isolatedcentro-temporal SW

VPA Language delay

12 F CAE (I) FC 11 AcousticandTactile

generalizedmyoclonic jerks

Yes FC normal in wakefulnessand sleep

VPA Normal

13 M None Normal 9 AcousticandThermal

generalizedmyoclonic jerks

No None normal in wakefulnessand sleep

none Normal

14 M FC (II) Normal 12 AcousticandTactile

generalizedmyoclonic jerks

No None normal in wakefulnessand sleep

none Normal

Please cite

this article

in press

as: Verrotti,

A., et

al., Refl

ex m

yoclonic epilepsy

in infancy:

A m

ulticenter clinical

study.Epilepsy

Res. (2012),

http://dx.doi.org/10.1016/j.eplepsyres.2012.07.004

AR

TIC

LE

IN P

RE

SS

+Model

EPIRES-4793;

No.

of Pages

8

Reflex

myoclonic

epilepsy in

infancy

5

15 M GTCS (I) Normal 6 Acoustic generalizedmyoclonic jerks

Yes None normal in wakefulnessand sleep

VPA Normal

16 M None Normal 3 Acoustic generalizedmyoclonic jerks

No None normal in wakefulnessand sleep

VPA Normal

17 F None Normal 14 AcousticandTactile

generalizedmyoclonic jerks

No None wakefulness: normal;sleep: generalized PSWdischarges

VPA Normal

18 M None Normal 10 Tactile generalizedmyoclonic jerks

No None normal in wakefulnessand sleep

VPA Normal

19 M None Normal 9 Acoustic generalizedmyoclonic jerks

No None normal in wakefulnessand sleep

VPA Normal

20 F None Normal 15 AcousticandTactile

generalizedmyoclonic jerks

Yes None normal in wakefulnessand sleep

VPA Normal

21 M FC (I) Normal 8 Tactile generalizedmyoclonic jerks

No None wakefulness: normal;sleep: generalized PSWdischarges

VPA Normal

22 F None Normal 10 Tactile generalizedmyoclonic jerks

No None normal in wakefulnessand sleep

VPA Normal

23 M None Normal 6 Tactile generalizedmyoclonic jerks

No None normal in wakefulnessand sleep

none Normal

24 M None Normal 9 Tactile generalizedmyoclonic jerks

No None normal in wakefulnessand sleep

VPA Normal

25 F None Normal 18 Tactile generalizedmyoclonic jerks

No None normal in wakefulnessand sleep

VPA Normal

26 F None Normal 12 Tactile generalizedmyoclonic jerks

No None normal in wakefulnessand sleep

VPA Normal

27 M FC (I) Normal 7 Acoustic generalizedmyoclonic jerks

No None normal in wakefulnessand sleep

VPA Normal

28 F None Normal 11 AcousticandTactile

generalizedmyoclonic jerks

No None normal in wakefulnessand sleep

VPA Normal

29 F FC (II) Normal 10 AcousticandTactile

generalizedmyoclonic jerks

Yes None wakefulness: normal;sleep: generalized PSWdischarges

VPA Normal

30 F None Normal 16 Acoustic generalizedmyoclonic jerks

No None normal in wakefulnessand sleep

VPA Normal

31 F IGE (II) Normal 12 Tactile generalizedmyoclonic jerks

Yes None wakefulness: normal;sleep: generalized PSWdischarges

VPA Normal

I and II: first and second degree relatives; FC: febrile convulsions, IGE: idiopathic generalized epilepsy; GTCS: generalized tonic-clonic seizures; CAE: childhood absence epilepsy; JME:juvenile myoclonic epilepsy; PSW: polispike and wave, SW: spike and wave discharges; VPA: valproic acid; CZP: clonazepam; IQ: intelligence quotient.

ARTICLE IN PRESS+ModelEPIRES-4793; No. of Pages 8

6 A. Verrotti et al.

Figure 1 The electroclinical features occurred during ictal video-EEG. (A) Video photo: the patient is playing with toys and hermother suddenly touches her face with a balloon; (B—E) the patient immediately shows myoclonic jerks, involving the axis of theb nt op c bur

eFKvomMdaugSw

1w

ascde

m(

ody and the limbs, blinking and an upward-outward movemeolyspike and wave discharges, synchronous with brief rhythmi

As previously described (Ricci et al., 1995; Cuvelliert al., 1997; Giovanardi Rossi et al., 1997; Deonna, 1998;ernandez-Lorente et al., 1999; Zafeiriou et al., 2003;urian and King, 2003; Caraballo et al., 2003), seizures wereery short, consisting of a single generalized myoclonic jerkr pseudo-rhythmical jerks, repeated in clusters lasting noore than 5—10 s, occurring several times a day. ReflexS were elicited both in wakefulness and in sleep. If chil-ren knew about the stimulus, they did not experience thettack. In our series, seizures were elicited more often bynexpected acoustic stimuli; but sudden touch and MS trig-

Please cite this article in press as: Verrotti, A., et al., Reflex mEpilepsy Res. (2012), http://dx.doi.org/10.1016/j.eplepsyres.

ered by both tactile and acoustic stimuli were also present.pontaneous attacks were reported frequently in agreementith previous reports (Ricci et al., 1995; Cuvellier et al.,

tce

Table 2 Comparison between treated and untreated patients.

Duration of RMEI (months) Family h

Untreated patients 19.4a 4 FC

Treated patients 4.5 6 FC

5 IGE

FC: febrile convulsions, IGE: idiopathic generalized epilepsy; IQ: intella p < 0.05 vs treated patients.

f the limbs. Ictal EEG shows generalized high-amplitude 3 Hzsts on EMG activity.

997; Deonna, 1998; Caraballo et al., 2003). Photosensitivityas absent in all patients.

Interictal EEG showed normal background activity onwakening, while rare generalized discharges occurredpontaneously or were reflex during sleep. Ictal EEG washaracterized by generalized high-amplitude SW and PSWischarge at 3 Hz, synchronous with brief rhythmic bursts oflectromyographic (EMG) activity.

Therefore, some of our patients have not received treat-ent and MS disappeared spontaneously. Some authors

Ricci et al., 1995; Deonna, 1997) recommend not to treat

yoclonic epilepsy in infancy: A multicenter clinical study.2012.07.004

he children. In the treated patients VPA was the drug ofhoice and effective as monotherapy. Our study providesvidence that first line drug is VPA which controlled seizures

istory Personal history Psychomotor development

2 FC normal1 FC 2 language delay

1 borderline IQ

igence quotient.

IN+Model

o(

apiten

R

A

B

C

C

C

D

D

D

D

F

G

K

ARTICLEEPIRES-4793; No. of Pages 8

Reflex myoclonic epilepsy in infancy

in all treated patients. It is interesting to underline thatthe treated patients had a shorter persistence of seizures.Although, the untreated patients group was small, our dataunderline that VPA may be helpful to provide effectiveseizures control; this clinical efficacy and good tolerabil-ity of VPA observed in our treated patients suggest that thisanticonvulsant drug can be considered in the patients withfrequent seizures.

In a high percentage of our series, children showed ahomogeneous cognitive profile within the normal range andwithout significant discrepancy between verbal and perfor-mance skills. None of the children developed significantneuropsychological or behavioral problems, confirming thebenign cognitive outcome of this form of epilepsy.

Clinical and EEG findings allow to differentiate RMEI fromother epileptic syndromes with myoclonic manifestations(myoclonic-astatic epilepsy, Dravet syndrome, intractableinfantile epilepsy and neonatal myoclonic encephalopathy,West syndrome, Lennox—Gastaut syndrome) (Deonna, 1998)and/or neurometabolic disorders (Kurian and King, 2003).

Some authors (Dravet and Bureau, 2002; Auvin et al.,2006) do not support the RMEI’s designation as a separatesyndrome from MEI, considering a single clinical and noso-graphic syndrome. In agreement with many others (Ricciet al., 1995; Cuvellier et al., 1997; Deonna, 1998; Zuberi andO’Regan, 2006), we propose to differentiate these two clin-ical entities. Therefore, despite apparent similar findings,they differ in many ways: the most important differenceis the complete absence of provoking factors in MEI. More-over, children with RMEI never show falling attacks that canbe, common in MEI. RMEI has shorter duration than MEI (4years and 9 months for BMEI in the series of Dravet et al.)(Dravet et al., 1992), whereas the mean duration of RMEI inreported patients is 7.8 months. RMEI appears to have ear-lier onset than MEI: onset at 11 months in RMEI, whereasthe mean age at onset in MEI is 20 months. Pharmacologi-cal treatment with VPA appears to be more effective in RMEIthan in MEI. Patients with MEI often require long-term treat-ment and discontinuing therapy in MEI may cause seizuresto relapse (Giovanardi Rossi et al., 1997; Auvin et al., 2006).Cognitive outcome with neuropsychological difficulties ispresent in one-third of children affected by MEI (Manganoet al., 2005; Zuberi and O’Regan, 2006), while patients withRMEI have an excellent cognitive outcome, as showed in ourpatients.

RMEI also differs clearly from startle epilepsy(Commission on Classification and Terminology of theInternational League Against Epilepsy, 1989), a variableentity characterized by seizures and an excessive startlereaction to sudden stimuli that occurs across a wide agerange. It arises from brain damage, particularly hypoxic-ischemic pre- and perinatal lesions. Clinical and EEGpatterns are variable (partial, tonic, atonic, myoclonic);seizures are often untreatable (Yang et al., 2010).

Distinctive EEG and EMG findings also differentiate RMEIfrom nonepileptic manifestations characterized by an exces-sive startle response: hyperekplexia or startle disease. It isan autosomal dominant disease characterized by exagger-

Please cite this article in press as: Verrotti, A., et al., Reflex mEpilepsy Res. (2012), http://dx.doi.org/10.1016/j.eplepsyres.2

ated startle reflex and neonatal hypertonia. The EEG doesnot show epileptic discharges during attacks, although sud-den noises may evoke a negative vertex wave followed bya background desynchronization and by tonic EMG activity

M

PRESS7

riginating in the frontal muscles and descending to the legsZhou et al., 2002).

Present study suggests an excellent seizure controlnd cognitive development in both treated and untreatedatients. Age-dependency, peculiar clinical and EEG find-ngs, normal neuropsychological development suggest thathis rare clinical entity constitutes an early idiopathic gen-ralized epilepsy, which should be classified as a distinctosographic syndrome.

eferences

uvin, S., Pandit, F., De Bellecize, J., Badinand, N., Isnard, H.,Motte, J., Villeneuve, N., Lamblin, M.D., Vallée, L., theEpilepsy Study Group of the French Pediatric Neurology Soci-ety, 2006. Benign myoclonic epilepsy in infants: electroclinicalfeatures and long-term follow-up of 34 patients. Epilepsia 47,387—393.

erg, A.T., Berkovic, S.F., Brodie, M.J., Buchhalter, J., Cross,J.H., van Emde Boas, W., Engel, J., French, J., Glauser, T.A.,Mathern, G.W., Moshé, S.L., Nordli, D., Plouin, P., Scheffer,I.E., 2010. Revised terminology and concepts for organiza-tion of seizures and epilepsies: report of the ILAE Commissionon classification and terminology, 2005—2009. Epilepsia 51,676—685.

araballo, R., Cassar, L., Monges, S., Yepez, I., Galicchio, S., Cer-sosimo, R., Fejerman, N., 2003. Epilepsia mioclonica refleja dellactante: un nuevo sindrome epileptico reflejo o una variantede la epilepsia mioclonica benigna del lactante. Rev. Neurol. 36,429—432.

ommission on Classification and Terminology of the InternationalLeague against Epilepsy, 1989. Proposal for revised classifi-cation of epilepsies and epileptic syndromes. Epilepsia 30,389—399.

uvellier, J.C., Lamblin, M.D., Cuisset, J.M., Vallée, L., Nuyts, J.P.,1997. L’épilepsie myoclonique bénigne réflexe du nourrisson.Arch. Pédiatr. 4, 755—758.

eonna, T., 1998. Reflex Seizures with somatosensory precipitation.Clinical and Electroencephalographic patterns and differentialdiagnosis, with emphasis on reflex myoclonic epilepsy of infancy.In: Zifkin, B.G., Andermann, F., Beaumanoir, A., Rowan, A.J.(Eds.), Reflex Epilepsies and Reflex Seizures: Advances in Neu-rology. Lippincott-Raven Publishers, Philadelphia, pp. 193—206.

ravet, C., Bureau, M., Roger, J., 1985. Benign myoclonic epilepsyin infants. In: Roger, J., Dravet, C., Dreifuss, F.E., Wolf, P.(Eds.), Epileptic Syndromes in Infancy, Childhood and Adoles-cence. John Libbey, London, pp. 159—170.

ravet, C., Bureau, M., Roger, J., 1992. L’épilepsie myocloniquebénigne du nourrisson. In: Roger, J., Dravet, C., Dreifuss, F.E.,Perret, A., Wolf, P. (Eds.), Les Syndromes épileptiques del’enfant et de l’adolescent. John Libbey, London, pp. 67—74.

ravet, C., Bureau, M., 2002. Benign myoclonic epilepsy of infancy.In: Zifkin, B.G., Andermann, F., Beaumanoir, A., Rowan, A.J.(Eds.), Reflex Epilepsies and Reflex Seizures: Advances in Neu-rology. John Libbey, London, pp. 69—79.

ernandez-Lorente, J., Pastor, J., Carbonell, J., Aparicio-Meix,J.M., 1999. Epilepsia mioclonica benigna refleja de la infancia.A proposito de una nueva observacion. Rev. Neurol. 29, 39—42.

iovanardi Rossi, P., Parmeggiani, A., Posar, A., Santi, A., Santucci,M., 1997. Benign myoclonic epilepsy: long-term follow-up of 11new cases. Brain Dev. 19, 473—479.

urian, M.A., King, M.D., 2003. An unusual case of benign reflex

yoclonic epilepsy in infancy: A multicenter clinical study.012.07.004

myoclonic epilepsy of infancy. Neuropediatrics 34, 152—155.angano, S., Fontana, A., Cusumano, L., 2005. Benign myoclonic

epilepsy in infancy: neuropsychological and behavioural out-come. Brain Dev. 27, 218—223.

IN+ModelE

8

R

Y

Z

Z

Z

ARTICLEPIRES-4793; No. of Pages 8

icci, S., Cusmai, R., Fusco, L., Vigevano, F., 1995. Reflexmyoclonic epilepsy in infancy: a new age-dependent idiopathicepileptic syndrome related to startle reaction. Epilepsia 36,342—348.

ang, Z., Liu, X., Qin, J., Zhang, Y., Bao, X., Wang, S., Chang, X.,2010. Clinical and electrophysiological characteristics of startle

Please cite this article in press as: Verrotti, A., et al., Reflex mEpilepsy Res. (2012), http://dx.doi.org/10.1016/j.eplepsyres.

epilepsy in childhood. Clin. Neurophysiol. 121, 658—664.afeiriou, D., Vargiami, E., Kontopoulos, E., 2003. Reflex myoclonic

epilepsy in infancy: a benign age-dependent idiopathic startleepilepsy. Epileptic. Disord. 5, 121—122.

W

W

PRESSA. Verrotti et al.

hou, L., Chillag, K.L., Nigro, M.A., 2002. Hyperekplexia: a treat-able neurogenetic disease. Brain Dev. 24, 669—674.

uberi, S.M., O’Regan, M.E., 2006. Developmental outcome inbenign myoclonic epilepsy in infancy and reflex myoclonicepilepsy in infancy: a literature review and six new cases.Epilepsy Res. 70S, S110—S115.

yoclonic epilepsy in infancy: A multicenter clinical study.2012.07.004

echsler, D., 1991. The Wechsler Intelligence Scale for Children,third ed. The Psychological Corporation, San Antonio, TX.

echsler, D., 1997. The Wechsler Adult Intelligence Scale, third ed.The Psychological Corporation, San Antonio, TX.