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Aicardi syndrome with favorable outcome: Case report and review
Brain & Development 29 (2007) 443–446 www.elsevier.com/locate/braindev
Case report
Aicardi syndrome with favorable outcome: Case report and review S. Grosso a
a,*
, G. Lasorella b, A. Russo b, P. Galluzzi c, G. Morgese a, P. Balestri
a
Pediatrics Department, Pediatric Neurology Section, University of Siena, S. Maria alle Scotte Hospital, 53100 Siena, Italy b Department of Neurosurgery, Pediatric Ophthalmology Section, University of Siena, 53100 Siena, Italy c Unit of Diagnostic and Therapeutic Neuroradiology, Azienda Ospedaliera Senese, 53100 Siena, Italy Received 22 September 2006; received in revised form 13 November 2006; accepted 17 November 2006
Abstract Aicardi syndrome is a congenital disorder characterized by severe psychomotor retardation, corpus callosum agenesis, chorioretinal lacunae, and early-onset infantile spasms. The prognosis is generally poor for children with the classical form. We report a peculiar case of Aicardi syndrome characterized by corpus callosum hypoplasia, brain malformations with subependymal heterotopias, extensive chorioretinal lacunae, seizures, and normal cognitive functions. Therefore, the clinical picture of the syndrome is broader than originally described. Cognitive disorders should not be considered inevitable and the prognosis not ineludibly poor. Ó 2006 Elsevier B.V. All rights reserved. Keywords: Chorioretinal lacunae; Infantile Spasms; Epilepsy; Brain malformation
1. Introduction
2. Case report
Aicardi syndrome (AS) (OMIM 304050) is an Xlinked dominant disorder. Generally only females are affected, who typically present with early-onset infantile spasms, corpus callosum agenesis, and ‘‘punched out’’ chorioretinal lacunae [1,2]. Psychomotor retardation is usually severe and ranged from 2 to 36 months in a group of 77 AS patients aged between one and 25 years [3]. Variation in the phenotypic expression of AS has been observed [3,4]. Pathogenetically, it was not explained by skewed X-inactivation patterns. In recent years AS patients with a favorable outcome have been reported in the literature. Here we describe a patient with an AS diagnosis whose cognitive development was normal for her age. A review of the literature has also been performed.
A nine-year-old-female patient was the first child of healthy and unrelated parents. The patient was born after an uneventful delivery, with a birth weight of 3.4 kg (50° ct), length of 50 cm (50° ct), and head circumference of 34.5 cm (50° ct). Apgar scores were 10 and 10 after one and five minutes, respectively. Psychomotor development was normal as was language acquisition. At the age of four years she presented with two seizure episodes characterized by staring gaze and loss of contact, which lasted 2–3 min. She therefore came under our care. Auxologic parameters were in the normal range as were cognitive functions. Physical examination was normal. The patient underwent EEG investigation, which showed sporadic spike-wave complexes and paroxysmal slow waves in the parieto-occipital regions. Brain MRI detected corpus callosum hypoplasia associated with polymicrogyria of the parieto-occipital areas and subependymal heterotopias. Ophthalmologic examination revealed extensive hypopigmented chorioretinal lacunae in both fundi. In both
*
Corresponding author. Tel.: +39 0577 586546; fax: +39 0577 586143. E-mail address: [email protected] (S. Grosso). 0387-7604/$ - see front matter Ó 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.braindev.2006.11.011
444
S. Grosso et al. / Brain & Development 29 (2007) 443–446
Fig. 1. Fundi show chorioretinal confluent lacunae of more than five times the size of the diameter of the optic disc. Scattered areas of hypo- and hyperpigmentation can also been noted. Posterior pole is normal.
eyes the size of confluent lacunae was more than five times the size of optic disk diameter. Evoked visual potentials were proved normal, as were brainstem auditory evoked responses. Brunet–Lezine test showed normal cognitive functions. The child was placed under therapy with carbamazepine (CBZ) (40 mg/kg/d). Seizures were controlled during a period of three years. At the age of seven years she relapsed into daily seizure episodes of similar semiology. EEGs showed a sequence of spike-wave complexes on the parieto-temporo-occipital areas spreading to the other regions. Topiramate, levetiracetam, and benzodiazepines were subsequently administered to control the seizures. At the age of eight years the seizures were characterized by episodes of sudden and brief antiflexions of the head. Video-EEG monitoring was performed. Interictal EEG findings were similar to those previously observed. Ictal EEG showed brief high-voltage diphasic wave discharges followed by sequences of slow waves on the parieto-temporo-occipital regions lasting 2–3 s (data not shown). Ophthalmologic investigation showed bilateral chorioretinal lacunae that were unchanged in size (Fig. 1). Brain MRI confirmed the previous lesions (Fig. 2). The patient was placed under therapy with valproate and lamotrigine. WISC-R testing showed an IQ of 100. During the latter observation sporadic epileptic spasms were still present.
3. Discussion Aicardi syndrome as initially described is characterized by the triad of corpus callosum agenesis, spasms in flexion, and chorioretinal lacunae. It is generally asso-
ciated with a very poor outcome. Severe neuromotor retardation is commonly present with an almost absent acquisition of motor and language skills [1,2]. In one study, only one patient out of 77 reached a development level of three years [3]. Spasms in flexion usually occur in most patients within the first months of life (in the neonatal period in 18% of patients) [5]. Spasms were absent in five of 156 AS patients reported in the literature [6]. In six out of 186 AS patients the corpus callosum appeared normal on CT-scan. Chorioretinal lacunae were generally regarded as pathognomonic of the syndrome [1,2]. However, two girls affected by AS with absence of chorioretinal lacunae have been noted [6]. Therefore, whether all constituents of the triad are necessary for the diagnosis is being debated [6]. In recent years, six patients affected by AS presenting with a favorable outcome have been described [7–12]. However, none of these patients showed the classical AS triad (Table 1). Several prognostic factors have been considered. Patients having retinal lesions five times the size of the optic disc diameter show poorer cognitive outcome [13]. Better prognosis was observed in those patients with fewer ocular anomalies, particularly if one eye was spared [14]. Indeed, unilateral localization of the retinal anomalies and the absence of macroscopic migration disorders were considered by Prats Vinas et al. [12] to be the basis of the favorable cognitive development observed in their patient. The patient we have described showed normal psychomotor development despite the presence of extended and bilateral chorioretinal lacunae (Fig. 1), which, therefore, does not appear to be a prognostic factor indicting poor outcome, at least in the present patient. Available data do not support a direct
S. Grosso et al. / Brain & Development 29 (2007) 443–446
445
Fig. 2. (A and B) Axial IR-T1 weighted image. Bilateral polymicrogyria involving the parieto-occipital cortex and subependimal heterotopias (black arrow) are evident. Dilatation of the posterior horn of the lateral ventricles, prominent on the left side, is appreciated. (C and D) Sagittal T1-weighted image. Corpus callosum hypoplasia is noted.
relationship between cognitive development and the severity of brain malformations; for example, partial versus complete agenesis of the corpus callosum [15] and cortical heterotopias appear not to influence visual functions and psychomotor performance [9]. However, only one patient among those with favorable outcome [10] had complete corpus callosum agenesis, and the severity of brain malformation could be considered mild in all of them (Table 1). In the patient we have described, although polymicrogyria and subependymal heterotopias were present in the posterior regions of the brain, the corpus callosum was only mildly hypoplastic (Fig. 2). Finally, the value of epileptic seizures as a prognostic factor has also been questioned. Most cases of AS
exhibit a slow cognitive development, even when seizures are controlled [9]. However, only two patients among those with favorable outcome showed infantile spasms, which were rapidly controlled by therapy. In addition, hypsarrhythmia was not noted in any case, with EEG anomalies focal in nature (Table 1). Of course, the favorable outcome might be related to the mild severity of brain malformation affecting this group of patients. We feel that electroclinical anomalies may play a key role as a prognostic factor. In other words, it is possible that the good outcome observed in a small group of AS patients might depend on the fact that electroclinical anomalies, although present, do not evolve towards an epileptic encephalopathy picture, which, it is well known, is able to deteriorate psychomotor func-
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S. Grosso et al. / Brain & Development 29 (2007) 443–446
Table 1 Aicardi patients with favorable outcome References
Age (years)
Chorioretinal lacunae
Cognitive functions
Type of seizures
EEG anomalies
MRI features
Menezes et al. [10]
10
LD
IS, CPS
Left T discharges
Anterior CC hypoplasia
King et al. [11]
49
Scattered around posterior pole. Small in the right eye Large rounded in the right Small in the left eye Rare, small and bilateral
LD
Hemiclonic
NR
CC dysgenesis
Mild P-R
IS
Partial agenesis CC CC agenesis, cerebellar hypoplasia, cortical atrophy CC hypoplasia CC agenesis CC hypoplasia, P-O polimycrogyria, subependimal heterotopias
Yacoub et al. [12]
2.3
Matlary et al. [13]
6.6
Confluent in the right eye Small in the left eye
LD
Absent
Left F-T discharges Normal
Lee et al. [14] Prats et al. [15] Present case
0.6 2 9
Bilateral small and solitary Two lacunae in the left eye Extensive and bilateral lacunae
Normal Normal Normal
CPS, MS Absent CPS, ES
Bil C-P Normal Bil T-P-O
LD, learning disabilities; P-R, psychomotor retardation; IS, Infantile spasms; CPS, complex partial seizures; MS, myoclonic seizures; T, temporal lobe; NR, not reported; F-T, fronto-temporal; Bil, bilateral; C-P, centro-parietal; T-P-O, temporo-parieto-occipital; CC, corpus callosum; ES, epileptic spasms; P-O, parieto-occipital.
tions [16]. Of course, only the identification of a genetic marker will provide a firm answer about the clinical variability observed in AS [6]. In conclusion, the absence of a reliable genetic or biochemical marker results in the diagnosis of AS still based on clinical and neuroradiological grounds. The clinical phenotype of AS appears to be wider than originally described. Learning disabilities should not be considered inevitable and the prognosis not ineludibly poor. In fact, we report a patient with AS presenting with bilateral chorioretinal lacunae, epilepsy, brain malformations, and corpus callosum hypoplasia who displayed normal cognitive functions, which further expands the phenotype of that disorder.
References [1] Ai cardi J, Lefebvre J, Lerique Koechlin A. A new syndrome: spasms in flexion, callosal agenesis, ocular abnormalities. Electroencephalogr Clin Neurophysiol 1965;19:609–10. [2] Aicardi J. Aicardi syndrome. Brain Dev 2005;27:164–71. [3] Rosser TL, Acosta MT, Packer RJ. Aicardi syndrome: spectrum of disease and long-term prognosis in 77 females. Pediatr Neurol 2002;27:343–6. [4] Grosso S, Farnetani MA, Bernardoni E, Morgese G, Balestri P. Intractable reflex audiogenic seizures in Aicardi syndrome. Brain Dev 2006, [Epub ahead of print]. [5] Jeavons PM, Livet M. Le syndrome de West. In: Roger J, editor. Les syndromes epileptique de l’enfant e de l’adolesent. Paris: John Libbey; 1992. p. 53–66.
[6] Aicardi J. Callosal agenesis chorioretinal lacunae, absence of infantile spasms, and normal development: Aicardi syndrome without epilepsy? Dev Med Child Neurol 2005;47:364. [7] Menezes AV, Enzenauer RW, Buncic JR. Aicardi syndrome – the elusive mild case. Br J Ophthalmol 1994;78:494–6. [8] King AM, Bowen DI, Goulding P, Doran RM. Aicardi syndrome. Br J Ophthalmol 1998;82:457. [9] Yacoub M, Missaoui N, Tabarli B, Ghorbel M, Tlili K, Selmi H, Essoussi A. Aicardi syndrome with favorable outcome. Arch Pediatr 2003;10:530–2. [10] Matlary A, Prescott T, Tvedt B, Lindberg K, Server A, Aicardi J, Stromme P. Aicardi syndrome in a girl with mild developmental delay, absence of epilepsy and normal EEG. Clin Dysmorphol 2004;13:257–60. [11] Lee SW, Kim KS, Cho SM, Lee SJ. An atypical case of Aicardi syndrome with favorable outcome. Korean J Ophthalmol 2004;18:79–83. [12] Prats Vinas JM, Martinez Gonzalez MJ, Garcia Ribes A, Martinez Gonzalez S, Martinez Fernandez R. Callosal agenesis, chorioretinal lacunae, absence of infantile spasms, and normal development: Aicardi syndrome without epilepsy? Dev Med Child Neurol 2005;47:419–20. [13] Menezes AV, Lewis TL, Buncic JR. Role of ocular involvement in the prediction of visual development and clinical prognosis in Aicardi syndrome. Br J Ophthalmol 1996;80: 805–11. [14] Hopkins IJ. Aicardi syndrome with normal development progress, remission of epilepsy and bilateral intraventricular tumors. In: Arzimanoglou A, Goutieres F, editors. Trends in Child Neurology. Paris: John Libbey; 1996. p. 77–80. [15] Menezes AV, MacGregor DL, Buncic JR. Aicardi syndrome: natural history and possible predictors of severity. Pediatr Neurol 1994;11:313–8. [16] Dulac O. Epileptic encephalopathy. Epilepsia 2001;42(Suppl. 3): 23–6.
Case report
Aicardi syndrome with favorable outcome: Case report and review S. Grosso a
a,*
, G. Lasorella b, A. Russo b, P. Galluzzi c, G. Morgese a, P. Balestri
a
Pediatrics Department, Pediatric Neurology Section, University of Siena, S. Maria alle Scotte Hospital, 53100 Siena, Italy b Department of Neurosurgery, Pediatric Ophthalmology Section, University of Siena, 53100 Siena, Italy c Unit of Diagnostic and Therapeutic Neuroradiology, Azienda Ospedaliera Senese, 53100 Siena, Italy Received 22 September 2006; received in revised form 13 November 2006; accepted 17 November 2006
Abstract Aicardi syndrome is a congenital disorder characterized by severe psychomotor retardation, corpus callosum agenesis, chorioretinal lacunae, and early-onset infantile spasms. The prognosis is generally poor for children with the classical form. We report a peculiar case of Aicardi syndrome characterized by corpus callosum hypoplasia, brain malformations with subependymal heterotopias, extensive chorioretinal lacunae, seizures, and normal cognitive functions. Therefore, the clinical picture of the syndrome is broader than originally described. Cognitive disorders should not be considered inevitable and the prognosis not ineludibly poor. Ó 2006 Elsevier B.V. All rights reserved. Keywords: Chorioretinal lacunae; Infantile Spasms; Epilepsy; Brain malformation
1. Introduction
2. Case report
Aicardi syndrome (AS) (OMIM 304050) is an Xlinked dominant disorder. Generally only females are affected, who typically present with early-onset infantile spasms, corpus callosum agenesis, and ‘‘punched out’’ chorioretinal lacunae [1,2]. Psychomotor retardation is usually severe and ranged from 2 to 36 months in a group of 77 AS patients aged between one and 25 years [3]. Variation in the phenotypic expression of AS has been observed [3,4]. Pathogenetically, it was not explained by skewed X-inactivation patterns. In recent years AS patients with a favorable outcome have been reported in the literature. Here we describe a patient with an AS diagnosis whose cognitive development was normal for her age. A review of the literature has also been performed.
A nine-year-old-female patient was the first child of healthy and unrelated parents. The patient was born after an uneventful delivery, with a birth weight of 3.4 kg (50° ct), length of 50 cm (50° ct), and head circumference of 34.5 cm (50° ct). Apgar scores were 10 and 10 after one and five minutes, respectively. Psychomotor development was normal as was language acquisition. At the age of four years she presented with two seizure episodes characterized by staring gaze and loss of contact, which lasted 2–3 min. She therefore came under our care. Auxologic parameters were in the normal range as were cognitive functions. Physical examination was normal. The patient underwent EEG investigation, which showed sporadic spike-wave complexes and paroxysmal slow waves in the parieto-occipital regions. Brain MRI detected corpus callosum hypoplasia associated with polymicrogyria of the parieto-occipital areas and subependymal heterotopias. Ophthalmologic examination revealed extensive hypopigmented chorioretinal lacunae in both fundi. In both
*
Corresponding author. Tel.: +39 0577 586546; fax: +39 0577 586143. E-mail address: [email protected] (S. Grosso). 0387-7604/$ - see front matter Ó 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.braindev.2006.11.011
444
S. Grosso et al. / Brain & Development 29 (2007) 443–446
Fig. 1. Fundi show chorioretinal confluent lacunae of more than five times the size of the diameter of the optic disc. Scattered areas of hypo- and hyperpigmentation can also been noted. Posterior pole is normal.
eyes the size of confluent lacunae was more than five times the size of optic disk diameter. Evoked visual potentials were proved normal, as were brainstem auditory evoked responses. Brunet–Lezine test showed normal cognitive functions. The child was placed under therapy with carbamazepine (CBZ) (40 mg/kg/d). Seizures were controlled during a period of three years. At the age of seven years she relapsed into daily seizure episodes of similar semiology. EEGs showed a sequence of spike-wave complexes on the parieto-temporo-occipital areas spreading to the other regions. Topiramate, levetiracetam, and benzodiazepines were subsequently administered to control the seizures. At the age of eight years the seizures were characterized by episodes of sudden and brief antiflexions of the head. Video-EEG monitoring was performed. Interictal EEG findings were similar to those previously observed. Ictal EEG showed brief high-voltage diphasic wave discharges followed by sequences of slow waves on the parieto-temporo-occipital regions lasting 2–3 s (data not shown). Ophthalmologic investigation showed bilateral chorioretinal lacunae that were unchanged in size (Fig. 1). Brain MRI confirmed the previous lesions (Fig. 2). The patient was placed under therapy with valproate and lamotrigine. WISC-R testing showed an IQ of 100. During the latter observation sporadic epileptic spasms were still present.
3. Discussion Aicardi syndrome as initially described is characterized by the triad of corpus callosum agenesis, spasms in flexion, and chorioretinal lacunae. It is generally asso-
ciated with a very poor outcome. Severe neuromotor retardation is commonly present with an almost absent acquisition of motor and language skills [1,2]. In one study, only one patient out of 77 reached a development level of three years [3]. Spasms in flexion usually occur in most patients within the first months of life (in the neonatal period in 18% of patients) [5]. Spasms were absent in five of 156 AS patients reported in the literature [6]. In six out of 186 AS patients the corpus callosum appeared normal on CT-scan. Chorioretinal lacunae were generally regarded as pathognomonic of the syndrome [1,2]. However, two girls affected by AS with absence of chorioretinal lacunae have been noted [6]. Therefore, whether all constituents of the triad are necessary for the diagnosis is being debated [6]. In recent years, six patients affected by AS presenting with a favorable outcome have been described [7–12]. However, none of these patients showed the classical AS triad (Table 1). Several prognostic factors have been considered. Patients having retinal lesions five times the size of the optic disc diameter show poorer cognitive outcome [13]. Better prognosis was observed in those patients with fewer ocular anomalies, particularly if one eye was spared [14]. Indeed, unilateral localization of the retinal anomalies and the absence of macroscopic migration disorders were considered by Prats Vinas et al. [12] to be the basis of the favorable cognitive development observed in their patient. The patient we have described showed normal psychomotor development despite the presence of extended and bilateral chorioretinal lacunae (Fig. 1), which, therefore, does not appear to be a prognostic factor indicting poor outcome, at least in the present patient. Available data do not support a direct
S. Grosso et al. / Brain & Development 29 (2007) 443–446
445
Fig. 2. (A and B) Axial IR-T1 weighted image. Bilateral polymicrogyria involving the parieto-occipital cortex and subependimal heterotopias (black arrow) are evident. Dilatation of the posterior horn of the lateral ventricles, prominent on the left side, is appreciated. (C and D) Sagittal T1-weighted image. Corpus callosum hypoplasia is noted.
relationship between cognitive development and the severity of brain malformations; for example, partial versus complete agenesis of the corpus callosum [15] and cortical heterotopias appear not to influence visual functions and psychomotor performance [9]. However, only one patient among those with favorable outcome [10] had complete corpus callosum agenesis, and the severity of brain malformation could be considered mild in all of them (Table 1). In the patient we have described, although polymicrogyria and subependymal heterotopias were present in the posterior regions of the brain, the corpus callosum was only mildly hypoplastic (Fig. 2). Finally, the value of epileptic seizures as a prognostic factor has also been questioned. Most cases of AS
exhibit a slow cognitive development, even when seizures are controlled [9]. However, only two patients among those with favorable outcome showed infantile spasms, which were rapidly controlled by therapy. In addition, hypsarrhythmia was not noted in any case, with EEG anomalies focal in nature (Table 1). Of course, the favorable outcome might be related to the mild severity of brain malformation affecting this group of patients. We feel that electroclinical anomalies may play a key role as a prognostic factor. In other words, it is possible that the good outcome observed in a small group of AS patients might depend on the fact that electroclinical anomalies, although present, do not evolve towards an epileptic encephalopathy picture, which, it is well known, is able to deteriorate psychomotor func-
446
S. Grosso et al. / Brain & Development 29 (2007) 443–446
Table 1 Aicardi patients with favorable outcome References
Age (years)
Chorioretinal lacunae
Cognitive functions
Type of seizures
EEG anomalies
MRI features
Menezes et al. [10]
10
LD
IS, CPS
Left T discharges
Anterior CC hypoplasia
King et al. [11]
49
Scattered around posterior pole. Small in the right eye Large rounded in the right Small in the left eye Rare, small and bilateral
LD
Hemiclonic
NR
CC dysgenesis
Mild P-R
IS
Partial agenesis CC CC agenesis, cerebellar hypoplasia, cortical atrophy CC hypoplasia CC agenesis CC hypoplasia, P-O polimycrogyria, subependimal heterotopias
Yacoub et al. [12]
2.3
Matlary et al. [13]
6.6
Confluent in the right eye Small in the left eye
LD
Absent
Left F-T discharges Normal
Lee et al. [14] Prats et al. [15] Present case
0.6 2 9
Bilateral small and solitary Two lacunae in the left eye Extensive and bilateral lacunae
Normal Normal Normal
CPS, MS Absent CPS, ES
Bil C-P Normal Bil T-P-O
LD, learning disabilities; P-R, psychomotor retardation; IS, Infantile spasms; CPS, complex partial seizures; MS, myoclonic seizures; T, temporal lobe; NR, not reported; F-T, fronto-temporal; Bil, bilateral; C-P, centro-parietal; T-P-O, temporo-parieto-occipital; CC, corpus callosum; ES, epileptic spasms; P-O, parieto-occipital.
tions [16]. Of course, only the identification of a genetic marker will provide a firm answer about the clinical variability observed in AS [6]. In conclusion, the absence of a reliable genetic or biochemical marker results in the diagnosis of AS still based on clinical and neuroradiological grounds. The clinical phenotype of AS appears to be wider than originally described. Learning disabilities should not be considered inevitable and the prognosis not ineludibly poor. In fact, we report a patient with AS presenting with bilateral chorioretinal lacunae, epilepsy, brain malformations, and corpus callosum hypoplasia who displayed normal cognitive functions, which further expands the phenotype of that disorder.
References [1] Ai cardi J, Lefebvre J, Lerique Koechlin A. A new syndrome: spasms in flexion, callosal agenesis, ocular abnormalities. Electroencephalogr Clin Neurophysiol 1965;19:609–10. [2] Aicardi J. Aicardi syndrome. Brain Dev 2005;27:164–71. [3] Rosser TL, Acosta MT, Packer RJ. Aicardi syndrome: spectrum of disease and long-term prognosis in 77 females. Pediatr Neurol 2002;27:343–6. [4] Grosso S, Farnetani MA, Bernardoni E, Morgese G, Balestri P. Intractable reflex audiogenic seizures in Aicardi syndrome. Brain Dev 2006, [Epub ahead of print]. [5] Jeavons PM, Livet M. Le syndrome de West. In: Roger J, editor. Les syndromes epileptique de l’enfant e de l’adolesent. Paris: John Libbey; 1992. p. 53–66.
[6] Aicardi J. Callosal agenesis chorioretinal lacunae, absence of infantile spasms, and normal development: Aicardi syndrome without epilepsy? Dev Med Child Neurol 2005;47:364. [7] Menezes AV, Enzenauer RW, Buncic JR. Aicardi syndrome – the elusive mild case. Br J Ophthalmol 1994;78:494–6. [8] King AM, Bowen DI, Goulding P, Doran RM. Aicardi syndrome. Br J Ophthalmol 1998;82:457. [9] Yacoub M, Missaoui N, Tabarli B, Ghorbel M, Tlili K, Selmi H, Essoussi A. Aicardi syndrome with favorable outcome. Arch Pediatr 2003;10:530–2. [10] Matlary A, Prescott T, Tvedt B, Lindberg K, Server A, Aicardi J, Stromme P. Aicardi syndrome in a girl with mild developmental delay, absence of epilepsy and normal EEG. Clin Dysmorphol 2004;13:257–60. [11] Lee SW, Kim KS, Cho SM, Lee SJ. An atypical case of Aicardi syndrome with favorable outcome. Korean J Ophthalmol 2004;18:79–83. [12] Prats Vinas JM, Martinez Gonzalez MJ, Garcia Ribes A, Martinez Gonzalez S, Martinez Fernandez R. Callosal agenesis, chorioretinal lacunae, absence of infantile spasms, and normal development: Aicardi syndrome without epilepsy? Dev Med Child Neurol 2005;47:419–20. [13] Menezes AV, Lewis TL, Buncic JR. Role of ocular involvement in the prediction of visual development and clinical prognosis in Aicardi syndrome. Br J Ophthalmol 1996;80: 805–11. [14] Hopkins IJ. Aicardi syndrome with normal development progress, remission of epilepsy and bilateral intraventricular tumors. In: Arzimanoglou A, Goutieres F, editors. Trends in Child Neurology. Paris: John Libbey; 1996. p. 77–80. [15] Menezes AV, MacGregor DL, Buncic JR. Aicardi syndrome: natural history and possible predictors of severity. Pediatr Neurol 1994;11:313–8. [16] Dulac O. Epileptic encephalopathy. Epilepsia 2001;42(Suppl. 3): 23–6.