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Abstract

  1. Top of page
  2. Abstract
  3. Case report
  4. Discussion
  5. Conclusion
  6. References

This article reports on a female infant with Aicardi syndrome presenting with malignant migrating partial seizures from her first day of life. Initially, unilateral tonic seizures were seen with contralateral ictal electroencephalogram findings. Typically, these tonic seizures were accompanied by head and eye deviation and were followed by a tonic seizure on the other side of the body. At 6 months of age she developed epileptic spasms. She showed no motor development, did not respond to eye contact, and was nasogastric tube-fed. The epilepsy syndrome in this child is refractory to antiepileptic treatment and there is no psychomotor development. This case expands the phenotype of this catastrophic epileptic encephalopathy and suggests that the corpus callosum is not necessary for the ‘migration’ of partial seizures in this syndrome.

Twelve years ago Coppola et al.1 first described 14 infants with malignant migrating partial seizures in infancy. This age-related epileptic encephalopathy is characterized by seizure onset between the first week of life and 7 months of age.1,2 In its typical form, a partial seizure starts in one brain region and is followed by another seizure arising from another region in the same or in the other hemisphere. In an individual child, the sequence of seizures is sometimes very stereotypical.

At present, there is no detectable cause of malignant migrating partial seizures. Brain imaging studies do not indicate cortical malformations. Metabolic and genetic studies remain negative.3 This condition has a very poor prognosis with severe psychomotor developmental delay, and intractability to antiepileptic drugs4–7 and corticosteroids.6

Aicardi syndrome8 is almost exclusively seen in females (with the exception of males with two X-chromosomes9) and is an X-linked disorder characterized by severe learning disability*, epileptic spasms, chorioretinal lacunae, agenesis of corpus callosum, and sometimes cortical malformations. Epileptic spasms are seen early in the course of the disease; later (>6mo), partial (mainly involving eyes and face) and generalized seizures can occur.

This case report describes a female with Aicardi syndrome who presented first with malignant migrating partial seizures and later with epileptic spasms. This case illustrates the expanding phenotype of this rare epileptic syndrome and shows that the corpus callosum presumably does not play a major role in the pathogenesis of migrating partial seizures. The parents of the child consented to the publication of this case report.

Case report

  1. Top of page
  2. Abstract
  3. Case report
  4. Discussion
  5. Conclusion
  6. References

The patient is a 3-month-old female who experienced a seizure on the first day of her life. She was born to non-consanguineous parents. Pregnancy and delivery were normal.

The first seizure occurred when the mother started to feed her. She had a short lasting (<10 second) tonic contraction of the right arm. This seizure type was seen in the next days with increasing frequency (5–10 per day). At the age of 7 days, a seizure was seen for the first time over the left side of her body, but preceded by a tonic seizure on the right side. Phenobarbital treatment was started but without success.

When she was 5 weeks old, seizure frequency increased to 20 seizures per day that were still partial and ‘migrating’. At that time, the tonic seizures in the arms were accompanied by lateral deviation of head and eyes. These seizures were classified as frontal lobe seizures. Increasing feeding problems were noted; the child remained very hypotonic and no eye contact was observed at the age of 6 weeks. She was admitted to the hospital and valproic acid was started.

Extensive metabolic screening remained negative. Ophthalmological examination revealed a typical choreo-retinal lacuna in the right eye. Magnetic resonance imaging of the brain showed an absent corpus callosum, without other cortical malformations. At that time the diagnosis of Aicardi syndrome was made. Different antiepileptic drugs (vigabatrin, levetiracetam, topiramate, pyridoxine, clonazepam) were tried but without a lasting effect on the very frequent partial migrating seizures.

An interictal electroencephalogram (EEG) showed diffuse slowing of the background activity with multifocal (predominantly right temporal) epileptiform activity when awake and sleep.

Typically, at the age of 6 weeks, an initial ictal EEG pattern was seen over the left central region. The child showed a right-sided clinical seizure with tonic stiffening and clonic movements of the right arm and head deviation to the right side. After about 20 seconds, another ictal pattern started over the right frontal region. The child then showed a deviation of the head to the left with a seizure on the left side of her body. The whole episode lasted more than 80 seconds.

At the age of 6 months, epileptic spasms were seen, with generalized ictal EEG patterns. The background in the EEG was not organized, but did not show the typical hypsarrhythmic pattern.

The child did not show any progress in her development and still needs continuous tube feeding at the age of 1 year. She showed almost no spontaneous movement and there was no eye contact. She was admitted in the Epilepsy Centre, Pulderbos, Belgium for further (palliative) care.

Discussion

  1. Top of page
  2. Abstract
  3. Case report
  4. Discussion
  5. Conclusion
  6. References

To the authors’ knowledge, only 31 cases of malignant migrating partial seizures have been reported (Table I). The patient in this case report fulfils the criteria for malignant migrating partial seizures as originally proposed by Coppola et al:1 onset before 6 months of age, migrating focal motor seizures at onset, multifocal seizures which are intractable to conventional antiepileptic drugs, and severe psychomotor delay.

Table I.   Reported cases of malignant migrating partial seizures
Studies, number of patientsAge at seizure onsetSeizure frequencyAntiepileptic treatmentEpilepsy outcomeClinical outcome
  1. ACTH, adrenocorticotrophic hormone; AED, antiepileptic drug; B6, vitamin B6; BR, bromides; CBZ, carbamazepine; CLZ, clobazam; CNZ, clonazepam; CS, corticosteroids; DZP, diazepam; FA, folinic acid; GBP, gabapentin; IVIG, intravenous immunoglobulins; KD, ketogenic diet; LEV, levetiracetam; LTG, lamotrigine; MDZ, midazolam; NZP, nitrazepam; OXC, oxcarbazepine; PB, phenobarbital; PHT, phenytoin; PP, pyridoxal phosphate; PRM, primidone; STP, stiripentol; SUL, sulthiame; TPM, topiramate; TRH, thyrothrope releasing hormone; VGB, vigabatrin; VPA, valproic acid; ZNS, zonisamide.

Coppola et al.,1 n=141–10moVery frequentB6, CBZ, CLZ, CNZ, CS, NZP, PB, PHT, STP, VGB, VPATwo patients seizure free (STP + CNZ)Three patients died; three resumed psychomotor development; the rest had severe delay
Okuda et al.,5 n=21: 26d 2: 4moNo data available1: ACTH, B6, BR, CS, CNZ, DZP, KD, MDZ, PB, PHT, TRH, NZP, VPA. 2: ACTH, BR, CBZ, IVIG, KD, MDZ, NZP, PB, PRM, TRH, VPA, ZNS1: >95% seizure reduction with BR. 2: Seizure free with BRBoth recovered neurological development
Wilmshurst et al.,13 n=21: 3wks 2: 2moMultiple seizures in cluster1: ACTH, B6, CBZ, CS, CNZ, KD, LTG, NZP, PB, PHT, VGB. 2: B6, CBZ, CS, LTG, MDZ, NZP, PB, PHT, VGBIntractable for both1: Died at 9mo. 2: Died at 12mo
Veneselli et al.,7 n=31: 15d 2: 3mo 3. 3mo1 and 2: very frequent in cluster. 3: partial seizuresACTH, B6, CBZ, CNZ, PB, PHT, VGB, VPA1–2 seizures per month to 3–4 seizures per year1: Died at 7mo. 2: Severe encephalopathy. 3: Severe learning disability
Gross-Tsur et al.,4 n=21: 4mo 2: 3moSeizures in cluster1: AEDs including B6, GBP, PB. 2: Aggressive AED therapy including B61: Seizure free at age 4y 6mo. 2: Refractory seizures.1: Severe learning disability. 2: Died at 18mo
Marsh et al.,11 n=61d–3mo10–35 per day4 patients used 6 or more AEDs, 2 patients ACTH, 2 patients FA, 2 patients KD1 patient seizure free, 2 patients infrequent seizures, 3 intractableProfound psychomotor delay 1/5, one mild delay
Hemaimess et al.,10 n=11d (16h after birth)1–186 per dayB6, BR, CNZ, LEV, LTG, MDZ, PB, PHT, VGBOne seizure per dayDied at 14mo
Hahn et al.,14 n=13mo‘Frequent’B6, FA, KD, OXC, LEV, PB, PP, steroids, SUL, TPM, VGB, VPADaily seizutesNo psychomotor development
Current study: Jocic-Jakubi and Lagae, n=11d5–50 per dayB6, CNZ, LEV, PB, TPM, VPAIntractableSevere developmental delay

Regarding the age of seizure onset (first day of life) the patient is one of the youngest together with the patient recently reported by Hemaimess et al.10

Despite the use of older and newer antiepileptic drugs, seizures in malignant migrating partial seizures typically remain intractable, as in this patient. Coppola et al. described a positive therapeutic response in two patients treated with a combination of stiripentol and clonazepam.3 Successful control with bromide in two patients with malignant migrating partial seizures has also been reported by Japanese authors.5 In a study by Marsh et al.11 one patient was seizure free, two had infrequent seizures, and three remained intractable. More recently, Hemaimmes et al.10 observed one patient with good seizure control (one seizure per day) treated with levetiracetam.

Among the 31 reported children in various studies, eight have died. The other patients have severe psychomotor delay, except patients reported by Marsh et al.11 In that study only one patient developed profound psychomotor delay. In this respect, malignant migrating partial seizures can be considered as a true epileptic encephalopathy. It is to yet be determined why these partial seizures are so devastating.

Whether the severe outcome is mainly related to the high seizure frequency at a young age, or to a specific epileptogenic process (which may also explain the ‘migration’ of seizures) remains to be elucidated. The present case illustrates that this syndrome can also be seen in children with a developmental brain abnormality, such as Aicardi syndrome. Unilateral retinal abnormality was identified in this case, as was described in two of 15 children in a recent review paper on Aicardi syndrome.12

Conclusion

  1. Top of page
  2. Abstract
  3. Case report
  4. Discussion
  5. Conclusion
  6. References

As there is no (visible) corpus callosum in children with Aicardi syndrome, it indicates that the stereotypical ‘synchronization’ of the partial seizures over the two hemispheres does not require an intact corpus callosum. Therefore, it is difficult to understand how a first partial seizure on one side of the brain can induce another, seizure on the other side, and why this temporally-related pattern in a particular child remains the same in the course of the disease. It could be hypothesized that, for instance, the anterior commissure plays an important role in the ‘transfer’ of the seizure to the other hemisphere.

Footnotes
  • *

    North American usage: mental retardation

References

  1. Top of page
  2. Abstract
  3. Case report
  4. Discussion
  5. Conclusion
  6. References
  • 1
    Coppola G, Plouin P, Chiron C, Robain O, Dulac O. Migrating partial seizures in infancy: a malignant disorders with developmental arrest. Epilepsia 1995; 36: 101724.
  • 2
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  • 3
    Coppola G, Veggiotti P, Del Giudice EM, et al. Mutational scanning of potassium, sodium and chloride ion channels in malignant migrating partial seizures in infancy. Brain Dev 2006; 28: 7679.
  • 4
    Gross-Tsur V, Ben-Zeev B, Shalav RS. Malignant migrating partial seizures in infancy. Pediatr Neurol 2004; 31: 28790.
  • 5
    Okuda K, Yasuhara A, Kamei A, Araki A, Kitamura N, Kobayashi Y. Successful control with bromide of two patients with malignant migrating partial seizures in infancy. Brain Dev 2000; 22: 5659.
  • 6
    Perrone MV, Biancheri R, Di Rocco M, Veneselli E. Migrating partial seizure in infancy: two further cases. Eur J Pediatr Neurol 1999; 3: A43.
  • 7
    Veneselli E, Perrone MV, Di Rocco M, Gaggero R, Biancheri R. Malignant migrating partial seizures in infancy. Epilepsy Res 2001; 46: 2732.
  • 8
    Aicardi J, Lefebvre J, Lerique-Koechlin A. A new syndrome: spasm in flexion, callosal agenesis, ocular abnormalities. Electroencephalogr Clin Neurophysiol 1965; 19: 60910.
  • 9
    Aicardi J. Aicardi syndrome. In: GuerriniR, AndermannF, CanapicchiR, RogerJ, ZifkinBG, PfannerP, editors. Dysplasias of cerebral cortex and epilepsy. Philadelphia: Lippincott-Raven, 1996: 21116.
  • 10
    Hemaimess G, Kadhim H, Nassogne MC, Bonnier C, Van Rijckevorsel K. Levetiracetam in a neonate with malignant partial seizures. Pediatr Neurol 2006; 34: 5559.
  • 11
    Marsh E, Melamed SE, Barron T, Clancy RR. Migrating partial seizures in infancy: expanding the phenotype of a rare seizure syndrome. Epilepsia 2005; 46: 56872.
  • 12
    Palmér L, Zetterlund B, Hård A-L, Steneryd K, Kyllerman M. Aicardi syndrome: presentation of onset in Swedish children born in 1975–2002. Neuropediatrics 2006; 37: 15458.
  • 13
    Wilmshurst JM, Appleton DB, Grattan-Smith PJ. Migrating partial seizure in infancy: two new cases. J Child Neurol 2000; 15: 71722.
  • 14
    Hahn A, Heckel M, Neubauer BA. Pronounced microcephaly in a patient with malignant migrating partial seizures in infancy. Epileptic Disord 2007; 9: 947.