Journal of Child Neurology

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Migrating Focal Seizures in Infancy: Analysis of the Electroclinical Patterns in 17 Patients Roberto Horacio Caraballo, Elena Fontana, Francesca Darra, Laura Cassar, Francesca Negrini, Elena Fiorini, Hugo Arroyo, Stella Ferraro, Natalio Fejerman and Bernardo Dalla Bernardina J Child Neurol 2008; 23; 497 originally published online Jan 29, 2008; DOI: 10.1177/0883073807309771 The online version of this article can be found at: http://jcn.sagepub.com/cgi/content/abstract/23/5/497

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Original Article

Migrating Focal Seizures in Infancy: Analysis of the Electroclinical Patterns in 17 Patients

Journal of Child Neurology Volume 23 Number 5 May 2008 497-506 © 2008 Sage Publications 10.1177/0883073807309771 http://jcn.sagepub.com hosted at http://online.sagepub.com

Roberto Horacio Caraballo, MD, Elena Fontana, MD, Francesca Darra, MD, Laura Cassar, MD, Francesca Negrini, MD, Elena Fiorini, MD, Hugo Arroyo, MD, Stella Ferraro, MD, Natalio Fejerman, MD, and Bernardo Dalla Bernardina, MD We describe the electroclinical features, therapy, and long-term evolution of 17 patients with migrating focal seizures in infancy, and analyzed the charts of these patients seen between February 1985 and July 2005. Three different electroclinical patterns were recognized: (1) 8 cases with alternating simple focal motor seizures at onset. The ictal electroencephalography (EEG) pattern was characterized by recurrence of rhythmic focal spikes or rhythmic sharp activity in the Rolandic region; (2) 5 cases with complex focal seizures and progressive appearance of polymorphic δ-θ activity in 1 temporo-occipital region recurring independently; (3) 4 cases with focal complex seizures with motor

manifestations. Ictal EEG showed flattening or fast activity in 1 frontotemporal region followed by unilateral fast poly-spikes in alternating clusters in both hemispheres. The focal seizures were refractory to antiepileptic drugs, and all patients except 3 had severe developmental delay. Migrating focal seizures in infancy is a newly defined and rare, but underrecognized, epileptic encephalopathy.

T

study, we describe a series of 17 cases with migrating focal seizures in infancy, giving a detailed evaluation of the electroclinical patterns, therapy, and long-term follow-up.

he syndrome of migrating focal seizures in infancy is characterized by an onset before age 6 months of multifocal seizures, a characteristic ictal electroencephalography (EEG) pattern consisting of seizures that arise independently and sequentially from both hemispheres, that are refractory to antiepileptic drugs, and cause subsequent severe mental retardation.1,2 Until now, no etiologies have been found. In 3 patients, the genetic analysis of potassium (KCNQ2, KCNQ3), sodium (SCN1A, SCN2A), and chloride (CLCN2) ion channels did not show abnormalities.3 The syndrome has been proposed in the scheme of the International League Against Epilepsy Task Force on Classification and Terminology under the heading “syndromes in development.”4 Several series of patients have been published in recent years.2,5–8 In this retrospective From the Neurology Department, Children’s Hospital “Prof Dr Juan P. Garrahan” (RHC, LC, HA, NF); Child Neurology Department, Italian Hospital, Buenos Aires, Argentina (SF); and Child Neuropsychiatry Unit, University of Verona, Italy (EF, FD, FN, EF, BDB). Address correspondence to: Roberto Horacio Caraballo, MD, Neurology Department, Hospital de Pediatría “Prof Dr Juan P. Garrahan,” Combate de los Pozos 1881, CP 1245, Buenos Aires, Argentina; e-mail rhcaraballo @arnet.com.ar. Caraballo RH, Fontana E, Darra F, et al. Migrating focal seizures in infancy: analysis of the electroclinical patterns in 17 patients. J Child Neurol. 2008;23:497-506.

Keywords: bromide; epileptic encephalopathy; focal seizures; multifocal seizures; refractory epilepsy

Methods Between February 1, 1985, and July 31, 2005, 17 patients met the diagnostic criteria of migrating focal seizures in infancy.1 Gender; age at onset; personal and family history of epilepsy and febrile seizures; duration, manifestation, circadian distribution, and frequency of seizures; response to therapy; and final outcome were analyzed. Repetitive ictal and interictal EEG recordings and polygraphic EEG recordings were performed in all patients. A mean of 20 ± 8 EEGs were obtained, and a mean of 12 ± 5 seizures were analyzed for each patient. All seizures were registered by polygraphic EEGs, and the majority of the seizures were also documented by 12- to 24-hour video-EEG recordings. As this is a retrospective study, the EEG methodology may have differed between the centers. Clinical and neurological examinations and etiologies were analyzed. All patients underwent brain computed tomography (CT) scan, and 12 underwent magnetic resonance imaging (MRI; 2 with spectroscopy). Other studies, such as neurometabolic investigations and karyotyping, were 497


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performed as well. Neurometabolic analysis included serum ammonia, serum pyruvic and lactic acids, acyl carnitine profile, serum amino acids, biotinidase, serum copper, and urine organic acids. Cerebrospinal fluid lactate/piruvate (3 patients) and cerebrospinal fluid amino acids (2 patients) were studied. Skin (5 cases) and muscle (1 case) biopsies were also performed. Genetic testing for Alper’s syndrome was performed in 2 patients. Autopsies were not obtained.

Results General Characteristics A total of 17 patients (9 boys and 8 girls) were identified between 1985 and 2005 at the Gianbattista Rossi Hospital of Verona (10 patients), the Garrahan Hospital of Buenos Aires (6 patients), and the Italian Hospital of Buenos Aires (1 patient). All children were born after normal gestation, but 1 was premature. There were 2 patients who had a firstdegree relative with a history of febrile seizures, and 2 who had a first-degree relative with a history of epilepsy. Physical examination was unremarkable in all patients, and none of them was dysmorphic. In all patients, the neurological examination showed hypotonia after the seizures became refractory, but there were no other neurological abnormalities. Muscle tone at birth was apparently hypotonic, but difficult to define accurately. The initial head circumferences of the children ranged between the 15th and 75th percentiles for age. At onset, brain CT scans and MRIs were normal in 13 patients. Repetitive MRIs showed mildly increased cerebrospinal fluid and mild ventricular enlargement in 4, and a moderate degree of the same findings in 3. The MRIs showed mesial temporal sclerosis in 3 cases and cerebellar atrophy in 1. Electroretinogram and visual and auditory evoked potentials were normal in all cases, but somatosensory potentials showed a high-amplitude and prolonged latency in 4 patients. No etiologies were found. Characteristics of the Seizures The mean and median ages at the time of the first seizure were 40 days and 31 days, respectively (range, 1–60 days). Seizure frequency progressively increased over a period of 10 to 60 days (mean, 40 days). The first seizures were clonic focal and/or unilateral in 8 patients, often without significant consciousness impairment. Shortly after, they occurred in an alternating manner in both sides of the body; true generalization remained very rare. Complex focal seizures characterized by behavioral arrest, autonomic manifestations (such as apnea, flushing, or cyanosis), and simple oro-alimentary automatisms were the first ictal manifestation in the 9 remaining patients. In 4 of them, the complex focal seizures were associated with a strong motor component, and the motor seizures were

sometimes accompanied by severe autonomic manifestations. In these 4 cases, focal motor signs, including deviation of the head and eyes, and clonic twitches of the eyelids were almost always present. Soon after onset, the daily seizures became very frequent in all 17 patients, evolving into a status epilepticus in 15. Concomitantly, progressive psychomotor deterioration became evident in all children. All 8 patients with predominantly motor seizures developed erratic, subcontinuous, myoclonic jerks, asynchronously occurring in both sides of the body during wakefulness and disappearing during sleep. In the course of the evolution, the ictal clinical manifestations varied between 1 seizure and the other in the same child. The focal seizures occurred independently in both hemispheres, alternating or concomitantly, but asynchronously, in the latter case mimicking a falsely generalized seizure. The seizures lasted between 1 and 20 minutes, often recurring several times a day in prolonged clusters both while awake and during sleep. EEG Findings The interictal EEG at onset showed normal background activity even during sleep in all patients. The electroclinical pattern was variable according to seizure frequency, form of recurrence, and topography. Three different electroclinical patterns were found: In the first pattern, seen in 8 patients, the seizures were simple focal motor seizures characterized by frequent rhythmic jerks involving 1 arm, and lasting from several minutes to hours. Soon after, the seizures occurred at different moments in both sides of the body. The ictal EEG pattern was characterized by the recurrence of ample rhythmic focal spikes (Figure 1), or by rhythmic sharp activity in the θ to α frequency range involving the Rolandic region of the contralateral hemisphere (Figure 2). The ictal nature of this last activity was difficult to recognize in the absence of polygraphic recordings. The awake and sleep interictal EEG recordings sometimes remained normal for several months, except for a significant unilateral presence of slow waves in the background activity for many hours after long-lasting seizures. In the evolution of the syndrome, the seizures tended to occur asynchronously but concomitantly in both Rolandic regions. When nearly simultaneous (Figure 1), they induced progressive impairment of consciousness with subcontinuous asynchronous myoclonias involving mainly the orofacial muscles, with severe autonomic manifestations. In the second pattern, observed in 5 cases, the seizures were focal complex seizures characterized by behavioral arrest with lip cyanosis and oro-alimentary automatisms without obvious motor manifestations, and progressive appearance of a polymorphic δ-θ activity of variable amplitude in 1 temporo-occipital region on the EEG recording (Figure 3A). These seizures, that lasted from 1 to several minutes, tended to recur independently


Electroclinical Patterns of Migrating Focal Seizures in Infancy/ Caraballo et al

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Figure 1. A 1-month and 27-day-old girl, 20 seconds after seizure onset with right temporal rhythmic spikes. Six minutes and 40 seconds after onset, rhythmic spikes in left temporo-occipital regions appear. Eleven and 18 minutes after onset, asymmetric bilateral rhythmic spikes associated with arrhythmic myoclonias are shown.

Figure 2. An 8-month-old girl with rhythmic sharp activity in the θ to α frequency range involving the left Rolandic region associated with bilateral arrhythmic myoclonic jerks. One hour after seizure onset, the polygraphic-EEG recording shows bilateral rhythmic sharp activity in the θ to α frequency associated with more rhythmic myoclonic jerks. At 2 hours and 15 minutes after seizure onset, the seizure was stopped by intravenous diazepam. Downloaded from http://jcn.sagepub.com at UNIV OF WASHINGTON on August 8, 2009

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Figure 3. (A, B) A 12-day-old girl with partial complex seizures characterized by behavioral arrest with lip cyanosis and oro-alimentary automatisms without obvious motor manifestations related to the progressive appearance of a polymorphic δ-θ activity of variable amplitude in 1 temporo-occipital region. These seizures tend to recur from the onset and alternate in both hemispheres.

in both hemispheres from onset, frequently evolving into long-lasting clusters (Figure 3A and B). In the absence of an EEG recording, it was impossible to recognize the

hemisphere involved, as the clinical symptoms were not lateralizing. In the case of concomitant independent bilateral involvement, consciousness appeared to be more



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Figure 4. In a 9-month-old girl, the electroencephalography (EEG) ictal pattern shows an initial flattening or a small discharge of fast activity in the left frontotemporal region followed by a hemispheric discharge of ample fast poly-spikes.

clearly impaired. In these patients, the interictal abnormalities on the EEG were not clear; the background activity was progressively deteriorating with slow waves only when the seizures became subcontinuous. In the third pattern, found in 4 cases, the seizures were focal complex characterized by behavioral arrest, breathing modifications followed by eye and head deviation, and mostly unilateral tonic contractions. The prolonged tonic

phase was frequently accompanied by intense cyanosis and drooling. On the EEG, the ictal pattern was characterized by an initial flattening or a small discharge of fast activity in 1 frontotemporal region followed by a discharge of ample fast poly-spikes in 1 hemisphere (Figure 4). These seizures, lasting from 1 to 2 minutes, alternated in both hemispheres, and the same alternating seizures started to occur in clusters later in the evolution (Figures 4 and 5). The seizures were


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Figure 5. In the same patient as Figure 4 and on the same electroencephalography (EEG) recording, these seizures, lasting from 1 to 2 minutes, occur alternatingly in both hemispheres, but briefly after start to occur in clusters still involving both hemispheres alternatingly. They are followed by prolonged postictal hemispheric activity with slow waves interposed by ample isolated spikes.

followed by a prolonged postictal hemispheric slow-wave activity interposed by ample isolated spikes (Figure 5) that became bilateral when the alternating seizures in clusters involved both hemispheres. Sometimes the seizures occurred independently in both hemispheres, but the tonic phase was in some cases nearly simultaneous evolving into an asymmetric generalized seizure. In these 4 cases, brief subclinical

frontotemporal seizures were frequently observed, occurring independently in both hemispheres mainly during sleep (Figure 6). No differences in neurological or physical signs were found in relationship to these 3 electroclinical patterns. In Table 1, we show the electroclinical features and evolution of our patients with migrating focal seizures in infancy.



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Figure 6. In a 6-month-old girl, the polygraphic electroencephalography (EEG) recording shows frequent brief subclinical frontotemporal seizures occurring independently in both hemispheres mostly during sleep.

Follow-up Regardless of the type of seizure, all became very frequent within a month after onset occurring several times a day in long-lasting clusters or as a simple partial motor status. Concomitantly, the children became floppy and somnolent with feeding difficulties. All kinds of pharmacological treatments, including conventional and new antiepileptic drugs, biotin, folinic acid, pyridoxine, and adrenocorticotrophin, were indicated. Only 2 patients received bromide. Twelve patients needed general anesthetic treatment on 1 or more occasions. All children except 4 continued presenting very frequent seizures. All patients except 2 had progressive neurological deterioration with generalized hypotonia, loss of visual contact and grasping, and loss of other motor and social abilities. All patients except 3 developed microcephaly. Five patients died at 5, 15, 18, 48 months, and 6 years of age, respectively, due to intercurrent infections in 2, and status epilepticus in the others. Four children had a good evolution, and 2 patients responded well to bromide 124–600 mg/kg per day. One of these patients, a girl, became seizure free at 3 years of age, but remained severely mentally impaired. A boy of 3 years of age currently has only rare subclinical frontotemporal seizures during sleep (Figure 7). He has mild axial hypotonia and severe language impairment. A 1year-old boy responded well to levetiracetam 1000 mg/d and has slight psychomotor retardation. A girl who is now 21 years old responded well to adrenocorticotrophin at 1 year of age. This latter patient currently has a borderline

IQ, mild ataxia, and monthly complex focal seizures and erratic myoclonias. None of our patients were placed on the ketogenic diet. At the last evaluation after a mean follow-up of 6 years (range, 1–21 years), all children except 3 showed severe psychomotor retardation. Five patients died. A total of 8 patients present daily seizures, 3 have sporadic seizures, and 1 patient is currently seizure free. No association was found between the 3 electroclinical patterns and the outcome of the syndrome, and none of the EEGs predicted seizure outcome.

Discussion We present 17 patients with a probable normal development at onset, who presented with focal migrating seizures that were generally refractory to antiepileptic drugs and severe psychomotor delay of unidentified etiology before the age of 5 months. However, it is difficult to determine whether these patients did not have mental retardation previously to the onset of the seizures. Electroclinically, we recognized 3 patterns in the evolution of the syndrome. In the first pattern, the seizures are simple focal motor characterized by frequent rhythmic jerks involving 1 arm, lasting from several minutes to hours. Soon after, they start to occur at different moments in both sides of the body. The ictal EEG pattern is characterized by the recurrence of ample rhythmic focal spikes or by a rhythmic sharp activity in the θ to α


504


1

5

60

35

29

18

58

19

46

8

8

59

48

38

52

55

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

CFS

FMS

CFS

FMS

CFS-MC

FMS

FMS

CFS

CFS

CFS-MC

FMS

CFS-MC

FMS

FMS

CFS-MC

CFS

FMS

Type of Seizures at Onset

-

Yes

-

Yes

-

Yes

Yes

-

-

-

Yes

-

Yes

Yes

-

-

Yes

CPMS Independent and bilateral asynchronous Independent and bilateral asynchronous Alternating, independent and bilateral asynchronous Independent and bilateral asynchronous Independent and bilateral asynchronous Alternating, independent and bilateral asynchronous Independent and bilateral asynchronous Alternating, independent and bilateral asynchronous Independent and bilateral asynchronous Independent and bilateral asynchronous Independent and bilateral asynchronous Independent and bilateral asynchronous Alternating, independent and bilateral asynchronous Independent and bilateral asynchronous Independent and bilateral asynchronous Independent and bilateral asynchronous Independent and bilateral asynchronous

Electroclinical Patterns

Yes

δ-θ activity in TO-R

Yes Yes


Yes

δ-θ activity in TO-R Spikes and S-W in RR

Yes

Yes

Yes

Spikes and S-W in RR

Flattening, fast activity in FT-R


-

Yes



Yes

Yes

-

Yes

Yes






Yes

Yes

δ-θ activity in TO-R Flattening, fast activity in FT-R

Yes

SE


Ictal EEG Findings

Moderate increase CSF spaces Mild increase CSF spaces Mild ventricular enlargement Moderate ventricular enlargement

Mild ventricular enlargement Mild increase CSF spaces

Normal

Normal

MTS

Moderate ventricular enlargement Moderate ventricular enlargement

Moderate increase CSF spaces

Cerebellar atrophy

Mild ventricular enlargement

Moderate ventricular enlargement MTS

MTS

Imaging Findings

microcephaly,

microcephaly,

microcephaly,

microcephaly,

Hypotonia, microcephaly, SPR Hypotonia, SPR

Hypotonia, microcephaly, SPR Microcephaly SPR

Hypotonia, MPR Hypotonia, SPR Hypotonia, SPR Hypotonia, SPR

Hypotonia, microcephaly, SPR

Hypotonia, microcephaly, SPR Hypotonia, MPR


MPR


Hypotonia, microcephaly, PND Hypotonia, microcephaly, SPR Hypotonia, microcephaly, PND

Physical Examination

Electroclinical Features, Imaging Findings, and Evolution of 17 Patients With Migrating Focal Seizures in Infancy

Seizure free Daily seizures Daily seizures Died

Daily seizures Daily seizures

Daily seizures Died

Sporadic seizures

Daily seizures Sporadic seizures

Sporadic seizures Died

Daily seizures

Daily seizures

Died

Died

Evolution

NOTE: FMS = focal motor seizures; CFS = complex focal seizures; MC = motor component; CPMS = continuous partial motor seizures; S-W = sharp waves; RR = Rolandic region; TO-R = temporo-occipital region; FT-R = frontotemporal region; SE = status epilepticus; MTS = mesial temporal sclerosis; SPR = severe psychomotor retardation; MPR = moderate psychomotor retardation; EEG = electroencephalography; PND = paroxysmal nocturnal dyspnea; CSF = cerebrospinal fluid.

40

1

Patient

Mean Age at Onset (d)

Table 1.


Figure 7.

505

The ictal polygraphic electroencephalography (EEG) recording shows only rare subclinical frontotemporal seizures during sleep.

frequency range involving the Rolandic region of the contralateral hemisphere. This electroclinical pattern was initially described as continuous focal seizures in infancy by Dalla Bernardina et al.9 In the second pattern, the seizures are focal, characterized by behavioral arrest with lip cyanosis and oro-alimentary automatisms without obvious motor manifestations, and progressive appearance of polymorphic δ-θ activity of variable amplitude in 1 temporo-occipital region on the EEG recording. These seizures, lasting from 1 to several minutes, tend to recur independently from onset. In the third pattern, the seizures are focal, characterized by behavioral arrest, breathing modifications followed by eye and head deviation, and mostly unilateral tonic contractions. The prolonged tonic phase is frequently accompanied by intense cyanosis and drooling. The ictal EEG pattern is characterized by an initial flattening or a small discharge of fast activity in 1 frontotemporal region followed by a hemispheric discharge of ample fast poly-spikes. These seizures, lasting from 1 to 2 minutes, occur in an alternating manner in both hemispheres. Later in the evolution, these alternating seizures start to occur in clusters. Early recognition of these 3 electroclinical patterns is important for the diagnosis of the syndrome to start adequate and vigorous treatment. Polygraphic EEG recording, especially in the case of the first electroclinical pattern, is the best study to thoroughly identify the characteristics of the seizures and the concomitant EEG abnormalities. Two or 3 of the electroclinical patterns described above sometimes occurred at the same time in the same patient. The electroclinical picture of these patients is compatible with migrating focal seizures in infancy and is similar to the one described by Coppola et al.1 Additional

cases from Europe, Australia, Japan, and the United States have been published.2,5–7 The majority of cases with migrating focal seizures in infancy are refractory to antiepileptic drugs, but some patients have shown a good evolution2 or a near satisfactory response to treatment.5 A 3-month-old male and a 4-month-old female infant with migrating focal seizures in infancy were treated with potassium bromide (80 mg/kg per day) after conventional antiepileptic drugs failed to adequately control the seizures. The potassium bromide therapy resulted in complete control of the seizures in 1 patient, and more than 95% reduction in seizure frequency in the other.5 Recently, an infant with migrating focal seizures in infancy with onset in the neonatal period responded well to levetiracetam.10 In our series of patients, 1 child responded well to levetiracetam, another responded well to adrenocorticotrophin, and 2 cases responded well to bromides. Unfortunately, despite adequate seizure control, marked acquired psychomotor impairment remained, probably due to the late initiation of bromide treatment at 6 months and 2 years after seizure onset. The progressive decline of head circumference percentile, hypotonia, psychomotor deterioration, and focal seizures that have an origin in different places of the brain suggest a diffuse pathogenic mechanism of this syndrome. Cortical microdysgenesis could be another mechanism, but was ruled out by Coppola et al.1 Autopsy could not be performed in any of the deceased patients in our series. In our patients, mesial temporal sclerosis was found on subsequent brain MRIs. In 2 patients of the series by Coppola et al, autopsy findings were compatible with mesial temporal sclerosis as well. We believe these findings are a consequence of the prolonged and repetitive seizures rather than the cause of the epilepsy. It would be crucial to evaluate


506


these patients with last generation scanners from the onset of the disease and during follow-up to detect previous or new brain abnormalities. Alternative mechanisms to consider include a new metabolic disease, channelopathy, or genetic disease. Multifocal seizures, as occur in migrating focal seizures in infancy, typically originate in different regions of the same hemisphere and/or in both hemispheres. The multifocal and particular way of propagation of the seizures suggests that the entire cerebral cortex is abnormally excitable. Multifocal seizures in clusters are a common feature in early onset epilepsies, and they can be observed in other very different conditions, including benign neonatal and infantile seizures, as well.11–13 However, in patients with migrating focal seizures in infancy, the early onset of the seizures quickly followed by a particular electroclinical pattern that involves both hemispheres independently, are refractory to antiepileptic drugs and cause progressive neuropsychological impairment, representing a severe type of epileptic syndrome that may be due to a genetic predisposition. These findings suggest that multifocal and migrating seizures in clusters may be a particular way of propagation in the immature brain.14,15 In newborns and infants, the neuroanatomical, neurochemical, and bioelectric connections between the cortical and subcortical structures are immature. Axonal and dendritic ramifications and synaptic connections are not completely developed yet, and myelinization is limited to a few pathways that do not include the main hemispheric commissures.7 In the immature brain of the newborn, the facilitation of excitatory amino acid-mediated neurotransmission and the poor inhibitory effectiveness of γ-aminobutyric acid transmission together with the immaturity of the cortical/subcortical bioelectric connections might account for these particular seizure phenomena.14,15 As to the differential diagnosis, other refractory epileptic syndromes that start in the first year of life, such as early myoclonic encephalopathy, early infantile epileptic encephalopathy, West syndrome, and Dravet syndrome, should be considered. However, these syndromes present electroclinical features that are clearly different from migrating focal seizures in infancy. Regarding the known metabolic encephalopathies that may cause intractable infantile focal epilepsies, mitochondrial disorders, peroxisomal disease, selenium deficiency, glutathione synthetase deficiency, glucose transporter deficiency syndrome, and sulfite oxidase deficiency should be taken into account. Alper syndrome should also be considered.16 We believe that migrating focal seizures in infancy is a newly defined and rare, but under-recognized, epileptic syndrome. The syndrome may be included in the category of epileptic encephalopathies, as the refractory seizures and/or the multifocal EEG abnormalities cause neuropsychological impairment. The other possibility is that the

neuropsychological impairment is secondary to a progressive encephalopathy of unknown etiology rather than to an epileptic phenomenon associated with a particular type of epileptic syndrome. Early treatment with bromide should be considered to control the seizures and consequently avoid progressive cognitive impairment. A better recognition of this syndrome will allow the identification of possible etiologies and long-term prognosis.

References 1. Coppola G Plouin P, Chiron C, et al. Migrating partial seizures in infancy: a malignant disorder with developmental arrest. Epilepsia. 1995;36:1017-1024. 2. Marsh E, Melamed S, Barron T, Clancy R. Migrating partial seizures in infancy: expanding the phenotype of a rare seizure syndrome. Epilepsia. 2005;46:568-572. 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;28:76-79. 4. Engel J. A proposed diagnostic scheme for people with epileptic seizures and with epilepsy: report of the ILAE task force on classification and terminology. Epilepsia. 2001;42:796-803. 5. Okuda K, Yasuhara A, Kamei A, et al. Successful control with bromide of two patients with malignant migrating partial seizures in infancy. Brain Dev. 2000;22:56-59. 6. Wilmshurst J, Appleton B, Grattan-Smith P. Migrating partial seizures in infancy: two new cases. J Child Neurol. 2000;15: 717-722. 7. Veneselli E, Perrone MV, Di Rocco M, et al. Malignant migrating partial seizures in infancy. Epilepsy Res. 2001;46:27-32. 8. Gross-Tsur V, Ben-Zeev B, Shalev RS. Malignant migrating partial seizures in infancy. Pediatr Neurol. 2004;31:287-290. 9. Dalla Bernardina B, Colamaria V, Capovilla G, et al. Epilesia parziale continua del lattante. Bol Lega It Epil. 1987;58/59:101-102. 10. Hmaimess G, Kadhim H, Nassogne MC, et al. Levetiracetam in a neonate with malignant migrating partial seizures. Pediatr Neurol. 2006;34:55-59. 11. Vigevano F, Fusco L, Di Capua M, et al. Benign infantile familial convulsions. Eur J Pediatr. 1992;151:608-612. 12. Plouin P, Anderson VE. Benign familial and non-familial neonatal seizures. In: Roger J, Dravet C, Bureau M, Genton P, Tassinari CA, Wolf P, eds. Epileptic Syndromes in Infancy, Childhood and Adolescence. 3rd ed. London: J Libbey, 2002:3-14. 13. Caraballo R, Cersósimo R, Espeche A, Fejerman N. Benign familial and non-familial infantile seizure: study of 64 cases. Epileptic Disord. 2003;5:45-49. 14. Brooks-Kayal A, Pritchett D. Developmental changes in human gamma-aminobutyric acid, receptor subunit composition. Ann Neurol. 1993;34:687-693. 15. Wasterlain C, Shirasaka Y. Seizures, brain damage and brain development. Brain Dev. 1994;16:270-295. 16. Ishil K, Oguni H, Hayashi K, et al. Clinical study of catastrophic infantile epilepsy with focal seizures. Pediatr Neurol. 2002;27:369-377.
