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Benign myoclonic epilepsy in infancy followed by childhood absence epilepsy
Seizure 20 (2011) 727–730
Contents lists available at ScienceDirect
Seizure journal homepage: www.elsevier.com/locate/yseiz
Case report
Benign myoclonic epilepsy in infancy followed by childhood absence epilepsy Salvatore Mangano a,*, Antonina Fontana a, Chiara Spitaleri a, Giuseppa Renata Mangano b, Maurizio Montalto c, Federico Zara d, Aldo Barbagallo e a
Dipartimento Materno Infantile, Unita` di Neuropsichiatria Infantile, Universita ‘di Palermo, Italy Dipartimento di Psicologia, Universita` di Palermo, Italy c Unita` Operativa di Medicina del Sonno in Eta` Evolutiva, A.O. Ospedali Riuniti ‘‘Villa Sofia-Cervello’’, Palermo, Italy d Unita` Operativa di Neurogenetica, Dipartimento di Pediatria, Ospedale Gaslini, Genova, Italy e Unita` Operativa di Neuropsichiatria Infantile, ASP Palermo, Italy b
A R T I C L E I N F O
A B S T R A C T
Article history: Received 14 December 2010 Received in revised form 14 June 2011 Accepted 17 June 2011
Benign myoclonic epilepsy in infancy (BMEI) is a rare syndrome included among idiopathic generalized epilepsies (IGE) and syndromes with age-related onset. Recently, it has been shown that a few patients with BMEI later had other epilepsy types mainly IGE but never childhood absence epilepsy (CAE). We report a patient who at 11 months of age showed isolated myoclonic jerks occurring several times a day. The ictal video-EEG and polygraphic recording revealed generalized discharge of spike-wave (SW) lasting 1–2 s associated with isolated bilateral synchronous jerk involving mainly the upper limbs controlled by valproic acid (VPA). At 6 years and 8 months the child developed a new electroclinical feature recognized as CAE. The ictal EEG disclosed a burst of rhythmic 3 Hz generalized SW. Our case is the first patient with BMEI reported in the literature who later developed a CAE. This finding suggests a common neurobiological and genetic link between different age-related epileptic phenotypes. ß 2011 Published by Elsevier Ltd on behalf of British Epilepsy Association.
Keywords: Myoclonic epilepsy Epilepsy in infancy Idiopathic epilepsy Childhood absence epilepsy
1. Introduction Benign myoclonic epilepsy in infancy (BMEI) is a rare syndrome first described by Dravet and Bureau1 with about 160 patients reported in other studies on this subject.2–4 BMEI was included among idiopathic generalized epilepsies and syndromes with agerelated onset in ILAE Classification .5 BMEI is characterized by brief, generalized myoclonic seizures occurring, without other seizure types except rare simple febrile seizures (FS), within 3 years of age in developmentally normal children. However, some cases have a later onset up to 4 years 8 months. The ictal electroencephalogram (EEG) shows a generalized discharge of polyspikes, polyspikewaves, or spike-waves (SW). The interictal EEG is usually normal. Seizures are easily controlled by valproic acid (VPA) and disappear during childhood. Typically BMEI has good prognosis, however recent studies reported a less favourable cognitive outcome in a few cases.2,4,6,7 Long-term follow-up studies reported that a few children with BMEI after a seizure-free time interval developed other epileptic phenotypes, mainly IGE, such as rare generalized tonic–clonic seizures (GTCS), or juvenile myoclonic epilepsy (JME).2,4,8
* Corresponding author. Tel.: +39 091 6555400; fax: +39 091 6555027. E-mail address: [email protected] (S. Mangano).
We report a female child with BMEI which occurred at age 11 months, followed by childhood absence epilepsy (CAE) at 6 years and 8 months old. To the best of our knowledge this occurrence has never been previously described.
2. Case report The proband, a female child, was the first daughter born to healthy unrelated parents. Her family history was unremarkable with regard to neurological and psychiatric diseases except for FS of the sister and a maternal uncle. She was born at term following an uneventful pregnancy with a birth weight of 3300 kg. The postnatal course was uneventful until 11 months of age when she showed isolated myoclonic jerks involving mainly her arms and head, occurring several times a day which were misdiagnosed for five months. At 12 months she was able to walk with support, and at 17 months without support. She spoke her first word at 14 months, and at 30 months she produced two word-phrases. At age of 16 months she was referred to our Child Neuropsychiatric Department at the University of Palermo because the frequency of myoclonic jerks had increased to 20–30/die. On admission the ictal video-EEG and polygraphic recording revealed generalized discharge of SW lasting 1–2 s associated with an isolated bilateral synchronous jerk involving mainly the upper
1059-1311/$ – see front matter ß 2011 Published by Elsevier Ltd on behalf of British Epilepsy Association. doi:10.1016/j.seizure.2011.06.008
728
S. Mangano et al. / Seizure 20 (2011) 727–730
Fig. 1. Brief bilateral synchronous jerk related to generalized discharge of spike and wave complex.
limbs (Fig. 1). Interictal EEG during wakefulness and during sleep showed age appropriate background activity. The results of blood and urine examination were within normal range. On neurological examination, cranial nerves were unaffected, muscle tone and deep tendon reflexes were normal. In addition, the patient did not show specific minor facial or other physical anomalies. Thus clinical and laboratory data led to BMEI diagnosis which required VPA treatment at the dose of 30 mg/kg/die. The VPA (109 g/ml) induced a seizure control within 11 days, but generalized spike-wave discharges, unrelated to clinical seizures, were still detected on EEG recordings during drowsiness at 5 years and 8 months of age. This finding suggested a long lasting antiepileptic treatment. The psychomotor development, assessed using the Bayley Scales of Infant Development [BSID-II; Bayley14], showed that the Mental Developmental Index and Psychomotor Developmental Index were 76, both performances were classified as mildly delayed. At two years old she experienced a febrile seizure despite AED treatment. At 4 years of age a battery of standardized cognitive and neuropsychological tests was carried out to evaluate: intellectual functioning [Wechsler Preschool and Primary Scale of Intelligence,
WPPSI; Wechsler; Orsini and Picone15], language expressive and receptive abilities including word and sentence comprehension, sentence repetition, naming, morphological and phonological accuracy, sentence structure [Language Evaluation Test, TVL, Cianchetti and Sannio Fancello12], and visuospatial integration ability [Visual Motor Integration test, VMI, Beery and Buktenica13]. The WPPSI showed a full scale IQ of 75, Verbal IQ = 80 and Performance IQ = 74. Comparison of patient scores to published norms on tests of language evaluation showed that the performances on sentence repetition, naming, morpho and phonological accuracy, and sentence structure subtests were within 5%ile (lower average range). The performances on word and sentence comprehension subtests were poor being below 5%ile. Visualmotor integration ability was in the below average range (VMI = 84). A new intellectual assessment at 5 years and 9 months of age showed a full scale IQ-WPPSI of 71 with a slight difference between verbal IQ (77) and performance IQ (69). At the same session, a neuropsychological examination assessed: language (verbal fluency, naming, syntactic comprehension), verbal short term memory (digit span), verbal episodic memory (immediate and delayed word list recall, word pair learning), visual–spatial short term memory (Corsi Test), selective attention (attentional matrices) [Developmental Neuropsychological Battery, BVN 5-11, Bisiacchi17, and visual spatial integration ability VMI, Rey figure B copy16]. The comparison of patient scores to published norms on tests of the neuropsychological battery showed an even overall profile in the lower average range. Only visual motor integration abilities were very poor (standard score 60). In addition, the patient showed oppositional behaviour and fidgeting. At 6 years and 8 months old the child had a new seizure type characterized by motor arrest, eye staring, abrupt and severe impairment of consciousness lasting a few seconds at frequency of 10–15 daily. The ictal EEG disclosed a burst of rhythmic 3 Hz generalized SW lasting 10–12 s (Fig. 2) and the interictal EEG during wakefulness and during sleep showed age appropriate background activity. Because the clinical and EEG findings suggested childhood absence epilepsy and the plasma level of VPA was 47 g/ml, at a lower level of the normal range, the dose of VPA was increased but it was ineffective in seizure control. Thus, ESM was started in add-on at the dose of 10 mg/kg/die and the child became seizure free. In order to exclude associated cerebral lesions or genetic disorders in our patient we carried out a magnetic resonance imaging (MRI) study and genetic investigations. Brain MRI at 8 years of age did not show characteristic abnormalities. Cytogenetic analysis revealed 46 XX karyotype and the array-CGH analysis did not detect genomic rearrangements. 3. Discussion The electroclinical feature, the clinical course, the personal and family history of febrile seizure, the lack of chromosome rearrangements and of abnormalities on brain MRI of our patient lead us to a diagnosis of BMEI.2 Indeed, some long-term follow-up studies have shown that seizure control was achieved in all cases, usually after a short time from treatment onset, and VPA in monotherapy was effective in more than 80% of patients with BMEI.2,4,7,8 Conversely, generalized or focal SW discharges persisted during sleep for several years after seizure control and antiepileptic treatment was long-lasting in many cases.2,4,8 Furthermore, the cognitive and neuropsychological findings of our patient show an overall profile in the lower average range
S. Mangano et al. / Seizure 20 (2011) 727–730
729
Fig. 2. Burst of rhythmic 3 Hz generalized spike and wave complexes during absence seizure.
supporting our previous study.7 The cognitive difficulties, ranging from very mild to severe level, were described in 15% of patients with BMEI in some studies previously published.2–4,6,8 It is likely that longitudinal, wider, and formal neuropsychological assessments of all patients could detect more disabilities than those reported. The relation between cognitive outcome and the earlier seizure onset and/or the delay in the start of the treatment is not fully clear, so other unknown factors might play a role in the cognitive outcome of patients with BMEI.2,6–8 In addition, recent long-term follow-up studies are providing valuable information on seizure and EEG outcomes in this rare syndrome. In a recent review, Dravet and Bureau2 evaluated the follow-up of 79 cases (63 lasting 5 years) with BMEI reported in the literature. They found that generalized myoclonic seizures disappeared in all these cases and most patients were seizure-free within one year. Among these patients however, 13 developed other seizure types, later in life. Rare GTCS were reported in 11/13 patients, ˜ as whereas the remaining two patients, described by Prats-Vin et al.,9 manifested absences. One patient had a ‘‘petit mal status’’ at 10 years old, after the drug withdrawal and a free interval, the other patient had ‘‘brief absences with marked eyelid myoclonia controlled by ESM’’ at 11 years old. This data suggests that both patients might have been affected by juvenile absence epilepsy (JAE), but essential clinical information such as EEG findings were missing.
Another longitudinal study,8 mean period of 8 years 9 months, including 22 patients, reported that 4 patients developed occasional isolated convulsive seizures that were induced by IPS or TV screens in 3 and unprovoked in one. Furthermore, a long-term follow-up of 34 new patients with BMEI4 reported 9 patients developing seizures after the disappearance of the initial myoclonic seizures. Among them 5 patients showed FS, one had a GTCS after VPA discontinuation, 2 patients developed JME at the ages of 9 and 12 years, respectively. In another patient, cryptogenic partial epilepsy developed 12 months after a first generalized seizure at 6 years old. The later development of CAE detected in our patient provides additional data on the outcome of BMEI. Since both BMEI and CAE belong to idiopathic generalized epilepsy, the occurrence of these phenotypes in our patient likely reflects the dynamic agedependent expression of a common genetic factor rather than a casual association.8 The age-dependent transition from an epileptic phenotype to another is being increasingly recognized in different early-onset idiopathic epilepsies such as idiopathic occipital lobe epilepsy10 and benign familial neonatal infantile seizures11 and likely involves pathogenetic mechanisms superimposed on physiological processes regulating normal brain development. Our study indicates the need to further investigate the relationship between the two syndromes and to elucidate the pathogenetic mechanisms of the evolution of BMEI to CAE as well as any common neurobiological and genetic substrate.
730
S. Mangano et al. / Seizure 20 (2011) 727–730
Disclosure Prof. S. Mangano received research funds (ex 60%) from University of Palermo. The remaining Authors have no conflicts of interest. Acknowledgements We are grateful to Mr. Brinley Thomas for his assistance in checking the translation. References 1. Dravet C, Bureau M. The benign myoclonic epilepsy of infancy. Revue d’Electroence´phalographie et de Neurophysiologie Clinique 1981;11:438–44. 2. Dravet C, Bureau M. Benign myoclonic epilepsy in infancy. In: Roger J, Bureau M, Dravet C, Genton P, Tassinari CA, Wolf P, editors. Epileptic syndromes in infancy, childhood and adolescence. 4th ed. Paris: John Libbey Eurotext; 2005. p. 77–88. 3. Zuberi SM, O’Regan ME. Developmental outcome in benign myoclonic epilepsy in infancy and reflex myoclonic epilepsy in infancy: a literature review and six new cases. Epilepsy Research 2006;70:S110–5. 4. 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. 5. Commission on classification and terminology of the international league against epilepsy. Proposal for revised classification of epilepsies and epileptic syndromes. Epilepsia 1989;30:389–99. 6. Giovanardi Rossi P, Parmeggiani A, Posar A, Santi A, Santucci M. Benign myoclonic epilepsy: long-term follow-up of 11 new cases. Brain & Development 1997;19:473–9.
7. Mangano S, Fontana A, Cusumano L. Benign myoclonic epilepsy in infancy: neuropsychological and behavioural outcome. Brain & Development 2005;27:218–23. 8. Darra F, Fiorini E, Toccante L, Mastella L, Torniero C, Cortese S, et al. Benign myoclonic epilepsy in infancy (BMEI): a longitudinal electroclinical study of 22 cases. Epilepsia 2006;47(Suppl. 5):31–5. 9. Prats-Vinas JM, Garaizar C, Ruiz-Espinoza C. Benign myoclonic epilepsy in infants. Revista de Neurologia 2002;34(3):201–4. 10. Taylor I, Marini C, Johnson MR, Turner S, Berkovic SF, Scheffer IE. Juvenile myoclonic epilepsy and idiopathic photosensitive occipital lobe epilepsy: is there overlap? Brain 2004;127:1878–86. 11. Singh NA, Westenskow P, Charlier C, Pappas C, Leslie J, Dillon J, et al. BFNC Physician Consortium. KCNQ2 and KCNQ3 potassium channel genes in benign familial neonatal convulsions: expansion of the functional and mutation spectrum. Brain 2003;126:2726–37.
References for neuropsychological tests used in the study 12. Cianchetti C, Sannio Fancello G. TVL, Test di valutazione del linguaggio. Trento: Erickson; 1997. 13. Beery KE, Buktenica NA, Beery NA. Developmental test of visual-motor integration, italian standardization. Firenze: Giunti O.S.; 2000. 14. Bayley N. Bayley scales of infant development. 2nd ed. San Antonio, TX: Psychological Corporation; 1993. 15. Wechsler D. Wechsler Preschool and Primary Scales of Intelligence, WPPSI; Wechsler; 1976; Italian adaption. Orsini A, Picone L. Firenze: Giunti O.S.; 1996. 16. Rey A. Rey complex figure test (RCFT). Italian adaption. Firenze: Giunti O.S.; 1979. 17. Bisiacchi PS, Cendron M, Gugliotta M, Tressoldi PE, Vio C. BVN test 5–11. Batteria di Valutazione Neuropsicologica per l’Eta Evolutiva. Trento: Erickson; 2005.
Contents lists available at ScienceDirect
Seizure journal homepage: www.elsevier.com/locate/yseiz
Case report
Benign myoclonic epilepsy in infancy followed by childhood absence epilepsy Salvatore Mangano a,*, Antonina Fontana a, Chiara Spitaleri a, Giuseppa Renata Mangano b, Maurizio Montalto c, Federico Zara d, Aldo Barbagallo e a
Dipartimento Materno Infantile, Unita` di Neuropsichiatria Infantile, Universita ‘di Palermo, Italy Dipartimento di Psicologia, Universita` di Palermo, Italy c Unita` Operativa di Medicina del Sonno in Eta` Evolutiva, A.O. Ospedali Riuniti ‘‘Villa Sofia-Cervello’’, Palermo, Italy d Unita` Operativa di Neurogenetica, Dipartimento di Pediatria, Ospedale Gaslini, Genova, Italy e Unita` Operativa di Neuropsichiatria Infantile, ASP Palermo, Italy b
A R T I C L E I N F O
A B S T R A C T
Article history: Received 14 December 2010 Received in revised form 14 June 2011 Accepted 17 June 2011
Benign myoclonic epilepsy in infancy (BMEI) is a rare syndrome included among idiopathic generalized epilepsies (IGE) and syndromes with age-related onset. Recently, it has been shown that a few patients with BMEI later had other epilepsy types mainly IGE but never childhood absence epilepsy (CAE). We report a patient who at 11 months of age showed isolated myoclonic jerks occurring several times a day. The ictal video-EEG and polygraphic recording revealed generalized discharge of spike-wave (SW) lasting 1–2 s associated with isolated bilateral synchronous jerk involving mainly the upper limbs controlled by valproic acid (VPA). At 6 years and 8 months the child developed a new electroclinical feature recognized as CAE. The ictal EEG disclosed a burst of rhythmic 3 Hz generalized SW. Our case is the first patient with BMEI reported in the literature who later developed a CAE. This finding suggests a common neurobiological and genetic link between different age-related epileptic phenotypes. ß 2011 Published by Elsevier Ltd on behalf of British Epilepsy Association.
Keywords: Myoclonic epilepsy Epilepsy in infancy Idiopathic epilepsy Childhood absence epilepsy
1. Introduction Benign myoclonic epilepsy in infancy (BMEI) is a rare syndrome first described by Dravet and Bureau1 with about 160 patients reported in other studies on this subject.2–4 BMEI was included among idiopathic generalized epilepsies and syndromes with agerelated onset in ILAE Classification .5 BMEI is characterized by brief, generalized myoclonic seizures occurring, without other seizure types except rare simple febrile seizures (FS), within 3 years of age in developmentally normal children. However, some cases have a later onset up to 4 years 8 months. The ictal electroencephalogram (EEG) shows a generalized discharge of polyspikes, polyspikewaves, or spike-waves (SW). The interictal EEG is usually normal. Seizures are easily controlled by valproic acid (VPA) and disappear during childhood. Typically BMEI has good prognosis, however recent studies reported a less favourable cognitive outcome in a few cases.2,4,6,7 Long-term follow-up studies reported that a few children with BMEI after a seizure-free time interval developed other epileptic phenotypes, mainly IGE, such as rare generalized tonic–clonic seizures (GTCS), or juvenile myoclonic epilepsy (JME).2,4,8
* Corresponding author. Tel.: +39 091 6555400; fax: +39 091 6555027. E-mail address: [email protected] (S. Mangano).
We report a female child with BMEI which occurred at age 11 months, followed by childhood absence epilepsy (CAE) at 6 years and 8 months old. To the best of our knowledge this occurrence has never been previously described.
2. Case report The proband, a female child, was the first daughter born to healthy unrelated parents. Her family history was unremarkable with regard to neurological and psychiatric diseases except for FS of the sister and a maternal uncle. She was born at term following an uneventful pregnancy with a birth weight of 3300 kg. The postnatal course was uneventful until 11 months of age when she showed isolated myoclonic jerks involving mainly her arms and head, occurring several times a day which were misdiagnosed for five months. At 12 months she was able to walk with support, and at 17 months without support. She spoke her first word at 14 months, and at 30 months she produced two word-phrases. At age of 16 months she was referred to our Child Neuropsychiatric Department at the University of Palermo because the frequency of myoclonic jerks had increased to 20–30/die. On admission the ictal video-EEG and polygraphic recording revealed generalized discharge of SW lasting 1–2 s associated with an isolated bilateral synchronous jerk involving mainly the upper
1059-1311/$ – see front matter ß 2011 Published by Elsevier Ltd on behalf of British Epilepsy Association. doi:10.1016/j.seizure.2011.06.008
728
S. Mangano et al. / Seizure 20 (2011) 727–730
Fig. 1. Brief bilateral synchronous jerk related to generalized discharge of spike and wave complex.
limbs (Fig. 1). Interictal EEG during wakefulness and during sleep showed age appropriate background activity. The results of blood and urine examination were within normal range. On neurological examination, cranial nerves were unaffected, muscle tone and deep tendon reflexes were normal. In addition, the patient did not show specific minor facial or other physical anomalies. Thus clinical and laboratory data led to BMEI diagnosis which required VPA treatment at the dose of 30 mg/kg/die. The VPA (109 g/ml) induced a seizure control within 11 days, but generalized spike-wave discharges, unrelated to clinical seizures, were still detected on EEG recordings during drowsiness at 5 years and 8 months of age. This finding suggested a long lasting antiepileptic treatment. The psychomotor development, assessed using the Bayley Scales of Infant Development [BSID-II; Bayley14], showed that the Mental Developmental Index and Psychomotor Developmental Index were 76, both performances were classified as mildly delayed. At two years old she experienced a febrile seizure despite AED treatment. At 4 years of age a battery of standardized cognitive and neuropsychological tests was carried out to evaluate: intellectual functioning [Wechsler Preschool and Primary Scale of Intelligence,
WPPSI; Wechsler; Orsini and Picone15], language expressive and receptive abilities including word and sentence comprehension, sentence repetition, naming, morphological and phonological accuracy, sentence structure [Language Evaluation Test, TVL, Cianchetti and Sannio Fancello12], and visuospatial integration ability [Visual Motor Integration test, VMI, Beery and Buktenica13]. The WPPSI showed a full scale IQ of 75, Verbal IQ = 80 and Performance IQ = 74. Comparison of patient scores to published norms on tests of language evaluation showed that the performances on sentence repetition, naming, morpho and phonological accuracy, and sentence structure subtests were within 5%ile (lower average range). The performances on word and sentence comprehension subtests were poor being below 5%ile. Visualmotor integration ability was in the below average range (VMI = 84). A new intellectual assessment at 5 years and 9 months of age showed a full scale IQ-WPPSI of 71 with a slight difference between verbal IQ (77) and performance IQ (69). At the same session, a neuropsychological examination assessed: language (verbal fluency, naming, syntactic comprehension), verbal short term memory (digit span), verbal episodic memory (immediate and delayed word list recall, word pair learning), visual–spatial short term memory (Corsi Test), selective attention (attentional matrices) [Developmental Neuropsychological Battery, BVN 5-11, Bisiacchi17, and visual spatial integration ability VMI, Rey figure B copy16]. The comparison of patient scores to published norms on tests of the neuropsychological battery showed an even overall profile in the lower average range. Only visual motor integration abilities were very poor (standard score 60). In addition, the patient showed oppositional behaviour and fidgeting. At 6 years and 8 months old the child had a new seizure type characterized by motor arrest, eye staring, abrupt and severe impairment of consciousness lasting a few seconds at frequency of 10–15 daily. The ictal EEG disclosed a burst of rhythmic 3 Hz generalized SW lasting 10–12 s (Fig. 2) and the interictal EEG during wakefulness and during sleep showed age appropriate background activity. Because the clinical and EEG findings suggested childhood absence epilepsy and the plasma level of VPA was 47 g/ml, at a lower level of the normal range, the dose of VPA was increased but it was ineffective in seizure control. Thus, ESM was started in add-on at the dose of 10 mg/kg/die and the child became seizure free. In order to exclude associated cerebral lesions or genetic disorders in our patient we carried out a magnetic resonance imaging (MRI) study and genetic investigations. Brain MRI at 8 years of age did not show characteristic abnormalities. Cytogenetic analysis revealed 46 XX karyotype and the array-CGH analysis did not detect genomic rearrangements. 3. Discussion The electroclinical feature, the clinical course, the personal and family history of febrile seizure, the lack of chromosome rearrangements and of abnormalities on brain MRI of our patient lead us to a diagnosis of BMEI.2 Indeed, some long-term follow-up studies have shown that seizure control was achieved in all cases, usually after a short time from treatment onset, and VPA in monotherapy was effective in more than 80% of patients with BMEI.2,4,7,8 Conversely, generalized or focal SW discharges persisted during sleep for several years after seizure control and antiepileptic treatment was long-lasting in many cases.2,4,8 Furthermore, the cognitive and neuropsychological findings of our patient show an overall profile in the lower average range
S. Mangano et al. / Seizure 20 (2011) 727–730
729
Fig. 2. Burst of rhythmic 3 Hz generalized spike and wave complexes during absence seizure.
supporting our previous study.7 The cognitive difficulties, ranging from very mild to severe level, were described in 15% of patients with BMEI in some studies previously published.2–4,6,8 It is likely that longitudinal, wider, and formal neuropsychological assessments of all patients could detect more disabilities than those reported. The relation between cognitive outcome and the earlier seizure onset and/or the delay in the start of the treatment is not fully clear, so other unknown factors might play a role in the cognitive outcome of patients with BMEI.2,6–8 In addition, recent long-term follow-up studies are providing valuable information on seizure and EEG outcomes in this rare syndrome. In a recent review, Dravet and Bureau2 evaluated the follow-up of 79 cases (63 lasting 5 years) with BMEI reported in the literature. They found that generalized myoclonic seizures disappeared in all these cases and most patients were seizure-free within one year. Among these patients however, 13 developed other seizure types, later in life. Rare GTCS were reported in 11/13 patients, ˜ as whereas the remaining two patients, described by Prats-Vin et al.,9 manifested absences. One patient had a ‘‘petit mal status’’ at 10 years old, after the drug withdrawal and a free interval, the other patient had ‘‘brief absences with marked eyelid myoclonia controlled by ESM’’ at 11 years old. This data suggests that both patients might have been affected by juvenile absence epilepsy (JAE), but essential clinical information such as EEG findings were missing.
Another longitudinal study,8 mean period of 8 years 9 months, including 22 patients, reported that 4 patients developed occasional isolated convulsive seizures that were induced by IPS or TV screens in 3 and unprovoked in one. Furthermore, a long-term follow-up of 34 new patients with BMEI4 reported 9 patients developing seizures after the disappearance of the initial myoclonic seizures. Among them 5 patients showed FS, one had a GTCS after VPA discontinuation, 2 patients developed JME at the ages of 9 and 12 years, respectively. In another patient, cryptogenic partial epilepsy developed 12 months after a first generalized seizure at 6 years old. The later development of CAE detected in our patient provides additional data on the outcome of BMEI. Since both BMEI and CAE belong to idiopathic generalized epilepsy, the occurrence of these phenotypes in our patient likely reflects the dynamic agedependent expression of a common genetic factor rather than a casual association.8 The age-dependent transition from an epileptic phenotype to another is being increasingly recognized in different early-onset idiopathic epilepsies such as idiopathic occipital lobe epilepsy10 and benign familial neonatal infantile seizures11 and likely involves pathogenetic mechanisms superimposed on physiological processes regulating normal brain development. Our study indicates the need to further investigate the relationship between the two syndromes and to elucidate the pathogenetic mechanisms of the evolution of BMEI to CAE as well as any common neurobiological and genetic substrate.
730
S. Mangano et al. / Seizure 20 (2011) 727–730
Disclosure Prof. S. Mangano received research funds (ex 60%) from University of Palermo. The remaining Authors have no conflicts of interest. Acknowledgements We are grateful to Mr. Brinley Thomas for his assistance in checking the translation. References 1. Dravet C, Bureau M. The benign myoclonic epilepsy of infancy. Revue d’Electroence´phalographie et de Neurophysiologie Clinique 1981;11:438–44. 2. Dravet C, Bureau M. Benign myoclonic epilepsy in infancy. In: Roger J, Bureau M, Dravet C, Genton P, Tassinari CA, Wolf P, editors. Epileptic syndromes in infancy, childhood and adolescence. 4th ed. Paris: John Libbey Eurotext; 2005. p. 77–88. 3. Zuberi SM, O’Regan ME. Developmental outcome in benign myoclonic epilepsy in infancy and reflex myoclonic epilepsy in infancy: a literature review and six new cases. Epilepsy Research 2006;70:S110–5. 4. 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. 5. Commission on classification and terminology of the international league against epilepsy. Proposal for revised classification of epilepsies and epileptic syndromes. Epilepsia 1989;30:389–99. 6. Giovanardi Rossi P, Parmeggiani A, Posar A, Santi A, Santucci M. Benign myoclonic epilepsy: long-term follow-up of 11 new cases. Brain & Development 1997;19:473–9.
7. Mangano S, Fontana A, Cusumano L. Benign myoclonic epilepsy in infancy: neuropsychological and behavioural outcome. Brain & Development 2005;27:218–23. 8. Darra F, Fiorini E, Toccante L, Mastella L, Torniero C, Cortese S, et al. Benign myoclonic epilepsy in infancy (BMEI): a longitudinal electroclinical study of 22 cases. Epilepsia 2006;47(Suppl. 5):31–5. 9. Prats-Vinas JM, Garaizar C, Ruiz-Espinoza C. Benign myoclonic epilepsy in infants. Revista de Neurologia 2002;34(3):201–4. 10. Taylor I, Marini C, Johnson MR, Turner S, Berkovic SF, Scheffer IE. Juvenile myoclonic epilepsy and idiopathic photosensitive occipital lobe epilepsy: is there overlap? Brain 2004;127:1878–86. 11. Singh NA, Westenskow P, Charlier C, Pappas C, Leslie J, Dillon J, et al. BFNC Physician Consortium. KCNQ2 and KCNQ3 potassium channel genes in benign familial neonatal convulsions: expansion of the functional and mutation spectrum. Brain 2003;126:2726–37.
References for neuropsychological tests used in the study 12. Cianchetti C, Sannio Fancello G. TVL, Test di valutazione del linguaggio. Trento: Erickson; 1997. 13. Beery KE, Buktenica NA, Beery NA. Developmental test of visual-motor integration, italian standardization. Firenze: Giunti O.S.; 2000. 14. Bayley N. Bayley scales of infant development. 2nd ed. San Antonio, TX: Psychological Corporation; 1993. 15. Wechsler D. Wechsler Preschool and Primary Scales of Intelligence, WPPSI; Wechsler; 1976; Italian adaption. Orsini A, Picone L. Firenze: Giunti O.S.; 1996. 16. Rey A. Rey complex figure test (RCFT). Italian adaption. Firenze: Giunti O.S.; 1979. 17. Bisiacchi PS, Cendron M, Gugliotta M, Tressoldi PE, Vio C. BVN test 5–11. Batteria di Valutazione Neuropsicologica per l’Eta Evolutiva. Trento: Erickson; 2005.