Original Article

269

Etiology and Long-Term Outcomes of Late-Onset Infantile Spasms Liisa Metsähonkala1

Eija Gaily1

Leena Valanne2

1 Epilepsy Unit, Department of Pediatric Neurology, Helsinki University

Hospital, Helsinki, Finland 2 Medical Imaging Center, Helsinki University Hospital, Helsinki, Finland 3 Department of Neurosurgery, Helsinki University Hospital, Helsinki, Finland

Göran Blomstedt3 Address for correspondence Liisa Metsähonkala, MD, Epilepsy Unit, Department of Pediatric Neurology, Helsinki University Hospital, Box 280, HUS 00029, Finland (e-mail: liisa.metsahonkala@hus.fi; eija.gaily@hus.fi).

Abstract

Keywords

► epilepsy ► spasms ► focal cortical dysplasia

Objectives The purpose of the study was to evaluate the etiology and long-term outcomes of late-onset epileptic spasms (LOS). Methods This is a retrospective analysis of all consecutive patients seen at our center with onset of clusters of epileptic spasms between 1 and 3 years of age in 1995 through 2005. Results Overall, 17 children with LOS were identified. Overall, 14 children (82%) had structural etiology. Six patients received resective surgical treatment. Five had focal cortical dysplasia type 1 (FCD1) histology (29% of all the patients). Overall, 16 children were followed for 2 to 18 years. At the latest follow-up, seizure freedom was observed in 67% of the operated and in 50% of the nonoperated patients. Normal cognition or only mild mental deficiency was observed in nine patients (56%), of whom eight were seizure-free. All patients with intractable spasms had a severe mental deficiency. Conclusion The overall cognitive outcome of LOS was more favorable than in the previous reports and was associated with seizure freedom. FCD1 is a frequent etiology for LOS and the cognitive outcome of patients with FCD1 seemed to be favorable.

Background Epilepsy with late-onset epileptic spasms (LOS) refers to a syndrome in which the typical seizures are similar as in the infantile spasm syndrome but seizure onset occurs beyond the typical age.1 The proportion of late-onset spasms of all patients with clusters of epileptic spasms has been reported to be 2.5 to 15%.1–5 The identification of these patients is not always easy as the delay to the correct diagnosis of LOS has been reported to be as long as 25 months from the onset of the spasms.1,2 LOS shares features with Lennox–Gastaut syndrome (LGS); the age of onset is similar and clusters of spasms may occur in LGS, among other seizure types. In only a minority of the patients the LOS evolves into the classical

received November 17, 2014 accepted after revision April 1, 2015 published online June 9, 2015

LGS (0–16% of patients with LOS 1–2, 5) and seems thus to be a separate epileptic encephalopathy.1 In the study by Chen et al, patients with LOS differed both from the patients with typical West syndrome and no focal seizures and from patients with West syndrome and focal seizures but had more features in common with the latter group.3 The proportion of LOS cases with known structural–metabolic etiology is 50 to 70%1–5; prenatal in 18 to 40% and postnatal or perinatal etiology in 30 to 35%. Hypoxic–ischemic brain damage, extensive brain malformations such as lissencephaly, and herpes simplex encephalitis seem to be relatively common.2,3 Focal cortical dysplasia (FCD) was reported as a rare etiology for LOS in older studies.1–3 In a recent study, tuberous sclerosis was the etiology in 12%, diffuse cortical

© 2015 Georg Thieme Verlag KG Stuttgart · New York

DOI http://dx.doi.org/ 10.1055/s-0035-1554099. ISSN 0174-304X.

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Neuropediatrics 2015;46:269–276.

Etiology and Long-Term Outcomes of Late-Onset Infantile Spasms dysplasia in 18%, chromosomal aberration in 6%, and hypoxic– ischemic encephalopathy in 3% of cases.4 Spasms were controlled in 20 to 45% of the patients with LOS in previous studies.1,2,4,5 The cognitive outcome of patients with LOS was similar to that of West syndrome.3 Moderate or severe developmental delay was observed in 60 to 80% of the patients.1–3 In a recent study by Ronzano et al, 12.5% of the children with LOS had normal development, 47% mild-to-moderate delay, and 40.6% severe delay.4 We reviewed all patients with LOS in our center during 11 years. We were especially interested in the frequency of FCD as etiology for LOS, in the features of patients with focal cortical dysplasia type 1 (FCD1), and in the long-term seizure and cognitive outcome of LOS.

Patients and Methods This study was a retrospective analysis of children treated for LOS at the Epilepsy Unit of the Helsinki University Hospital which serves as the secondary referral center for a population of 1.5 million and a tertiary referral center for epilepsy surgery evaluations in Finland (population 5.3 million). The medical records of all patients with the diagnosis of epileptic spasms were retrospectively evaluated. LOS were defined as clusters of spasms starting between ages 12 and 36 months as in the study by Bednarek et al.1 Patients who had started to have LOS in 1995 through 2005 were included in this study. The initial diagnosis of clusters of epileptic spasms was done based on ictal video electroencephalography (EEG) in 16 patients. In one patient (patient number 2), the diagnosis was based on observation of the spasms by an experienced pediatric neurologist. The routine clinical protocol for diagnosis and for follow-up during the study period in our hospital was to perform a video-EEG recording lasting for 2 to 6 hours and including sleep and wake and at least 15 minutes after awakening. The spasms were categorized as symmetric or asymmetric based on the clinical features in the video confirmed by deltoid electromyography (EMG) in some of the patients. The diagnosis of spasms was classified as delayed if it took over 4 weeks from the reported start of the seizures and the diagnosis of spasms. The diagnosis of the other types of seizures was based on the history obtained from the medical records and in some cases, on video-EEG recordings. Seizures were classified according to the revised terminology and concepts of seizures and epilepsies6. The diagnostic video-EEGs were performed using Telefactor equipment with 10/20 electrode placement and bilateral deltoid EMG electrodes. For this study, the archived video-EEG samples were reevaluated by one of the authors (L.M.). The interictal background activity in the video-EEG was categorized into the following two groups: (1) no localizing features (hypsarrhythmia or multifocal independent spikes (MIS) or other multifocal or generalized epileptiformic findings with or without background slowing with no localizing features); and (2) localizing features of epileptiformic abnormalities (hemihypsarrhythmia or prominent focal epileptiform activity among the multifocal findings). Neuropediatrics

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Hypsarrhythmia was defined according to Watanabe et al7 as “an interictal paroxysmal discharge of random high-voltage slow waves and spikes of varying duration and location occurring continuously or in bursts of varying duration.” Pattern of MIS was diagnosed if three or more independent foci of spikes or sharp waves were seen against a background with less than 200 mV voltage.8 The ictal EEG changes were categorized as nonlocalizing or localizing. The findings of EEG studies preceding the video-EEG were also reviewed. All patients had at least one 1.5 Tesla cerebral magnetic resonance imaging (MRI) study. The routinely acquired sequences were T1 axial and sagittal, T2 axial and coronal, and axial flair. Five patients were also imaged with a 3.0 Tesla MRI scanner. All the MRI images were reanalyzed by an experienced pediatric neuroradiologist (third author, L.V.) who was blinded for the clinical and video-EEG findings. Etiology was categorized as structural–metabolic, genetic, or unknown based on the current International League against Epilepsy Classification.6 Data on seizure outcome and development were collected from the medical records. The time of cessation of spasms was based on the report of the parents and confirmation in videoEEG. Overall, 16 patients were followed for 2 to 18 years (5–20 years of age). No follow-up information was available for one patient. The routinely used methods in the follow-up were the Bayley Scales of Infant Development II (BSID-II)9 and the modified Finnish version of Münchener Funktionelle Entwicklungsdiagnostik-method10 for children younger than 2 years of age and Wechsler Intelligence Scale for ChildrenRevised11 for older children. Cognitive outcome according to the latest developmental evaluation is presented using five categories (normal, specific learning difficulties with IQ in the normal range, mild, moderate, and severe mental deficiency) and is based on the psychometric tests. The histological diagnosis was based on the contemporary classification12 instead of the new classification by the ILAE.13 As a retrospective study, there was no study-related protocol for antiepileptic medication. The clinical routine in our center for infantile spasm syndrome in 1995 to 2005 was to start with either adrenocorticotropin or vigabatrin, and if there was no response, then to switch to the other. This study was approved by the joint Ethical Committee of Helsinki University and Helsinki University Hospital. Written informed consent was received from the carriers of the children for acquiring follow-up information from other hospitals.

Statistical Methods Fisher exact test was used for the comparisons between groups based on cognitive outcome (normal-to-mild mental deficiency versus moderate-to-severe mental deficiency). A p < 0.05 was considered significant.

Results A total of 17 children fulfilled the criteria for LOS during the study period. Overall, 10 were male (58%). The mean age at the onset of the clusters of spasms was 19.1 months (standard

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deviation, 5.3 months; boys 16.6 months; and girls 22.7 months). Overall, 14 children had a structural–metabolic etiology for epilepsy (82%). In three patients, the etiology was unknown. Summary of clinical, imaging, and video-EEG data of the 16 patients with follow-up information is shown in ►Table 1. Seizures. Four children had asymmetric spasms. In five patients, spasms were the only seizure type. Four children had presented with other seizure types before the onset of epileptic spasms (mean age at epilepsy onset 8.5 months, in two of the children the onset of epilepsy was acute symptomatic [patient numbers 3 and 5]). Eight children started to have other types of seizures after spasm onset (►Table 1). EEG-findings at the diagnosis of spasms. Four children had hypsarrhythmia and one had hemihypsarrhythmia in the video-EEG. Interictal EEG abnormalities were nonlocalizing in five (29%). Overall, 12 patients showed localizing interictal EEG findings (hemispheric or focal predominance in multifocal epileptiform activity) (71%). Focal ictal EEG findings were seen in five patients, one of whom also had asymmetric spasms. Asymmetric spasms and localizing interictal EEG findings were typical for patients with FCD1. MRI findings. Overall, 14 children (82%) had abnormal MRI. Focal/regional gray–white matter blurring or increased signal in the white matter suggesting FCD was found in six patients (35%), five frontal and one occipitotemporal (►Fig. 1, the interictal and ictal EEG findings of these patients are presented in ►Fig. 2). In addition, one patient had an unspecific frontal MRI lesion (abnormal white matter signal, patient number 11). One patient had lissencephaly. Two patients had vascular lesions: one showed sequela of a prenatal hemorrhage in the white matter and the other had a postnatal infarction of the middle cerebral artery associated with pneumococcal encephalitis at the age of 10 months. Four patients had generalized cerebral atrophy; one of them had a history of herpes simplex virus encephalitis at the age of 2 weeks, two had undefined encephalopathy with abnormal development from birth and one had cartilage-hair hypoplasia. Three patients had normal MRI; one of them (patient number 12) had focal findings on other investigations and followed by epilepsy surgery (see later). Delay in diagnosis of LOS. The median delay for the diagnosis of epilepsy in the patients was 3 weeks (mean 8 weeks, maximum 12 months). The median delay in diagnosis of clusters of spasms was 4 weeks from the onset of spasms (mean 5.4 months, maximum 18.7 months). In eight patients (47%), the diagnosis was delayed (> 4 weeks from the onset of spasms [patient numbers 4, 7, 9–11, and 14–16]). Seizure outcome (including the operated patients). A total of 16 patients were followed up for 2 to 18 years (►Table 1). One patient died of an infectious disease at the age of 6 years (patient number 16). Two patients still had spasms at the time of the last follow-up (12.5%). Spasms continued for 1 month to 10 years (median 13 months). Spasms ceased in less than 3 months in four patients. Five patients had other types of seizures at the time of last follow-up (31%). Nine patients were seizure-free (56%), four postsurgery. In none of the patients, the epilepsy evolved into typical LGS.

Metsähonkala et al.

Epilepsy surgery. Six patients were operated (►Table 1). The resections were sublobar in five and multilobar in one (patient number 15). Of the MRI positive patients, four8,10,13,14 patients received resections guided by noninvasive localizing methods and intraoperative corticography and one (patient number 9) underwent a stereo-EEG investigation. The epileptic network proved to extend from the lesional area to the insular and frontobasal cortex and involved also the motor cortex. The resection was a large frontobasalfronto-opercular and anterior insular resection. Three patients remained seizure-free after the first operation. One (patient number 15) relapsed with focal seizures 19 months after a temporoparietal multilobar resection at the age of 4 years. She had stereo-EEG at the age of 14 years, followed by a second operation (posterior multilobar resection). She has been seizure-free since but the follow-up is only 12 months. One patient (patient number 10) was initially seizure-free but relapsed at 34 months with short focal seizures. The only MRI negative patient (patient number 12) who was operated, underwent a subdural grid recording, after which a left posterior temporal resection was performed at the age of 18 years. The resection was suboptimal because of the overlapping eloquent cortex. He was seizure-free for 3 months and then relapsed with focal seizures. The histological finding in five of six operated patients was FCD1a15. In one patient (patient number 9), additional eosinophilic cytoplasmic inclusions were seen in the glial cells. In one patient (patient number 12), no histological diagnosis could be made because of the insufficient sample size. There were no permanent complications related to the operations. One patient (patient number 15) had a postoperative hemiplegia which resolved in 2 months. One patient with preoperative learning difficulties (patient number 12) showed a temporary decline in the complex verbal functions. One patient (patient number 15) had a postoperative subgaleal hydrocephalus which needed shunting after the second operation. Cognitive outcome. In the latest evaluation of the cognitive development, four patients had severe-to-profound mental deficiency (25%), three had moderate mental deficiency (19%), six had a mild mental deficiency (37.5%), one had specific learning difficulties (6%), and two patients had normal cognitive development (12%). Patients with favorable cognitive outcome (normal/learning difficulties or mild mental deficiency) were significantly more often seizure-free than children with poor-cognitive outcome. All patients with intractable spasms had severe mental deficiency. The age at onset of spasms, the delay in diagnosis or the time for cessation of spasms did not differ between the cognitive outcome groups (►Table 2). None of the patients with FCD1 or unknown etiology had severe mental deficiency at the latest evaluation. In two operated patients (patient numbers 8 and 15), cognitive development stagnated for 1 year preoperatively and started to progress postoperatively.

Discussion FCD1 was found to be a frequent etiology (30% of all patients) for late-onset spasms. Both the seizure outcome and the Neuropediatrics

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13/male/16

15/male/11

16/male/8

18/male/15

18/male/8

18/female/5

18/female/11

18/female/16

19/female/15

20/male/20

23/male/6

26/female/14

30/female/14

30/female/6 (until death)

3

4

5

No. 4/2015

6

7

8

9

10

11

12

13

14

15

16

ss, aa, t

as, (f)

ss, aa, fs

ss

ss, (fm)

ss, tc, (fm)

as, (fm)

as

ss, t

as

ss, tc, aa, fm

ss, tc

ss, m, (tc)

ss, tc, fm

ss, (at)

ss

Seizure types

Nonlocalizing

Nonlocalizing

Nonlocalizing

Left frontal

Nonlocalizing

Left frontocentral

Right frontal

Nonlocalizing

Right frontal (F4)

Nonlocalizing

Nonlocalizing

Nonlocalizing

Nonlocalizing

Lateralized, right hemisphere

No ictal EEG

Nonlocalizing

Ictal EEG at spasm onset

MIS

MIS right TO predominant

Focal spikes right CP, generalized slowing

Focal spikes and slowing, left FT, GPSP in sleep

MIS and slowing, left posterior predominant

Bilateral FSSW, focal spikes left FT

Focal spikes, right F, GSW in sleep

Focal spikes, left F, bilateral O slowing

MIS, right F predominant

Hyps, focal spikes, left FT

Focal spikes (left O), generalized slowing

Hyps, right predominant

Hyps

Hemi-hyps, right

MIS, background slowing and β

Hyps

Interictal EEG

Atrophy, (cartilage–hair hypoplasia)

Right TO FCD (FCD1a)

Mild atrophy (unidentified syndrome)

Left F FCD (FCD1a)

Normal (unknown)

Left F focal lesion

Right F FCD (FCD1a)

Left F FCD (FCDIa)

Right F FCD (FCDIa)

Left F lesion indicating FCD

Normal (unknown)

Generalized atrophy (HSV encephalitis)

Normal (unknown)

Right tissue loss (MCA infarct)

Lissencephaly

Right P periventricular leukomalacia (perinatal hemorrhage)

MRI (etiology)

Yes (4 and 14 y)

Yes (4 y)

Yes (18 y)

Yes (11 y)

Yes (9 y)

Yes (3 y)

Surgery (age at surgery)

Died at 6 y, never sz free

sf postop follow-up 12 mo

Seizures

sf post-op

Seizures, focal motor

sf for 7 y, off AED

sf post-op for 2.5 y, relapse with fm

sf post-op

sf post-op

sf for 3 y, on AED

sf for 6 y, on AED

tc seizures

Spasms

sf for 15 y, no AED

Spasms

sf for 7 y, no AED

Seizure outcome

Moderate md

Mild md (14 y)

Severe md (7 y)

Mild md (6 y)

Learning difficulties (19 y)

Normal (13 y)

Moderate md (12 y)

Mild md (9 y)

Mild md (5 y)

Mild md (8 y)

Mild md (13 y)

Severe md (3 y)

Severe md (3 y)

Moderate md (15 y)

Severe md (3 y)

Normal (6 y)

Cognitive outcome (age at latest testing)

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Etiology and Long-Term Outcomes of Late-Onset Infantile Spasms

Abbreviations: aa, atypical absence; AED, antiepileptic medication; as, asymmetric spasms; at, atonic; CP, centroparietal; EEG, electroencephalography; f, focal; F, frontal; fs, febrile seizures, in italic if onset before spasms, in parenthesis if started more than 1 year after the start of the spasms; FCD, focal cortical dysplasia; FCD1a, focal cortical dysplasia type I; fm, focal motor; FSSW, frontal slow spike and wave; FT, frontotemporal; fu, follow-up; GPSP, generalized polyspikes; GSW, generalized spike waves; Hyps, hypsarrhythmia, HSV, herpes simplex virus;; m, myoclonic; M, male; MCA, middle cerebral artery; md, mental deficiency; MIS, multifocal independent spikes; MRI, magnetic resonance imaging; O, occipital; P, parietal; post-op, postoperative; seizures, only other types of seizures continue; sf with med, seizure-free with medication; sf with op, seizure-free after operation; spasms, spasms continue; ss, symmetric spasms; SSW, slow spike waves; t, tonic; tc, tonic–clonic; TO, temporo-occipital.

13/male/18

13/male/9

2

1

Age at onset (mo)/gender/fu age (y)

Table 1 Detailed characteristics of 16 patients with late-onset infantile spasms

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cognitive outcome of patients with LOS were better than in the previous studies. Cognitive outcome was especially good in the seizure-free patients. The cognitive outcome of the children with FCD1 was surprisingly good even with drugresistant epilepsy which had lasted for years. For the etiology of epilepsy, in general, our findings were in agreement with the previous studies on both LOS and on typical infantile spasms. A structural–metabolic etiology was found in 82% of the patients in this study. The proportion of LOS cases

with known structural–metabolic etiology is 50 to 70%.1–5 The proportion of symptomatic etiology for infantile spasm syndrome varies from 60 to 90%, being 81% in a population-based study from Finland.14 Periodic spasms were described as an epileptic seizure type in focal epilepsy already in 1987 by Gobbi et al.14 Cerebral malformations have been reported to account for 25 to 30% of the etiology of infantile spasms15–17 and clusters of spasms have been described to frequently co-occur with other types of seizures in infants with FCD.18 In a recent study by Kang

Fig. 2 (A) Interictal and ictal electroencephalography (EEG) findings of patient 9 at the age of 5 years. (B) Interictal and ictal EEG findings of patient 8 at the age of 2.8 years. (C) Interictal and ictal EEG findings of patient 15 at the age of 3 years. Neuropediatrics

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Fig. 1 (A) Axial T2 image (3 T) of patient number 9 at the age of 5 years. Blurring of gray and white matter junction suggesting focal cortical dysplasia (FCD) is seen on the fronto-opercular region on the left. Histological diagnosis was FCDIa and eosinophilic inclusions in the glial cells. (B) Axial T2 image (1.5 T) of patient number 8 at the age of 2.8 years. Blurring of gray and white matter junction suggesting FCD on the right frontal region. Histological diagnosis was FCD1a. (C) Coronal T2 image (1.5 T) of patient 15 at the age of 3 years. Blurring of gray and white matter junction in the right temporo-occipital region and abnormal signal and shape in the right hippocampus. Histological diagnosis was FCD1a.

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Fig. 2 (Continued)

et al, MRI based or histological diagnosis of FCD was found in 12.6% of patients with infantile spasm and the histological diagnosis was FCD1 in 75% of the operated patients.19 As well, FCD was a frequent etiology for patients in a surgical series on LGS.20 In one of our patients, in addition to FCD1, eosinophilic cytoplasmic inclusions were seen in the glial cells. Similar Neuropediatrics

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findings have been reported earlier in patients with drugresistant epilepsy.21,22 One of our patients had cartilage–hair hypoplasia. Epilepsy is seen only infrequently in this genetic syndrome and cortical atrophy is not a typical feature. It is possible that her epilepsy was not related to her genetic syndrome.

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Table 2 Characteristics of patients classified according to the cognitive outcome Normal

Mild MD/learning diff

Moderate MD

Severe MD

N

2

7

3

4

Mean age at onset, mo (SD)

16 (4)

21 (4)

20 (9)

17.5 (6)

Delayed diagnosis (> 1 mo), N

1

3

2

2

Mean duration of spasms, mo (SD)

5.5 (5)

32 (38)

65 (87)

10 (continue in 2)

FCD1 (histological diagnosis)

0

4

1

0

Seizure free at latest follow-up

2

6

1

0

Other structural etiology

2

0

2

4

Unknown

0

3

0

0

Etiology

Even though FCD is a frequent etiology for other epileptic encephalopathies, FCD was described as an etiological factor only in a single case in the older reports on LOS.1–3 In the study by Ronzano et al,4 MRI-based diagnosis of diffuse cortical dysplasia was found in 18% of children with LOS. The high proportion of FCD in the study by Ronzano and our series might be because of the advanced MRI diagnostics. Also both of these series are small and patients suitable for epilepsy surgery are overrepresented. In our study, three of the patients with FCD had been referred from elsewhere for epilepsy surgery evaluation. The overrepresentation of the patients suitable for epilepsy surgery could also contribute to the outcome results. Most of the FCDs in our study were frontal. Also, in the study by Ronzano et al,4 the focal interictal EEG findings were anterior in 76% of the cases. These observations are in line with the findings by Koo and Hwang23 who showed that frontal lesions initiate clusters of epileptic spasms later than lesions in other localizations and suggested that this could partially be explained by later maturation of the frontal cortex. However, both of these series too small for strong conclusions. In a recent study by de la Vaissière et al,24 11 patients with drug-resistant epileptic spasms and results of their intracranial recordings and surgery are described. Five of their patients had LOS. One of these five had a frontal FCD1 as etiology for the epilepsy and the rest had either temporal or parietal dysembryoplastic neuroepithelial tumors as etiology for epilepsy. Both the outcome of spasms and the cognitive outcome of the children were better in our study in comparison to previous studies. In this study, 25% had severe and 19% moderate developmental delay at the time of the latest follow-up. In previous studies, moderate or severe developmental delay was described in 60 to 80% of the patients.1–3 In a recent study by Ronzano et al,4 12.5% of the children with LOS had normal development, 47% mild-to-moderate delay, and 40.6% severe delay. Seizure freedom (either with antiepileptic medication or surgery) was associated with good cognitive outcome in our study. In patients with infantile spasm, cryptogenic etiology, short treatment lag, good initial

response to treatment, and seizure freedom in the follow-up have been shown to associate with favorable long-term cognitive outcome.25 In none of our patients did the epilepsy evolve into LGS. In the previous studies, 0 to 16% of the children with LOS have developed LGS.1,2,5 It could be that with longer follow-up the evolvement to LGS would be seen more frequently. However, in our study and also in the previous studies several children with 5- to 10-year followup no such evolvement was seen. We could not find any significant differences between the cognitive outcome groups in the delay of diagnosis or response to treatment, possibly partially because of the small number of patients. The delay of the diagnosis was reasonably short for most of the patients indicating a good cooperation between the primary and secondary health care in Finland. However, for some patients, the diagnosis was difficult and was done only based on the ictal video-EEG. An unexpected result was that none of the patients with FCD1 or unknown etiology had severe mental deficiency even though they suffered from treatment-resistant seizures for years. Six of our patients with LOS have been operated on and the histological diagnosis was FCD1 in five of them. Four patients with FCD1 have been seizure-free after a lobar or sublobar resection. Two patients went through a stereo-EEG recording and one through a subdural grid recording presurgically. Only one patient had epileptic spasms during the time of the intracranial investigation. As described by others, the epileptic network related to spasms was extensive.24 The surgical outcome of our patients is surprisingly good considering that the surgical outcome of children with FCD1 is generally found poor because of the heterogeneous etiology and extensive involvement of multiple lobes.26 Seizure freedom has been reported in 21 to 46% of children with isolated FCD1.26,27 Our observations emphasize the role of FCD1 as an etiology for LOS. These patients have risk for drug-resistant epilepsy, but their long-term cognitive outcome seems to be quite favorable. Our data confirm the previous findings indicating that frontal lesions provoke spasms later than lesions elsewhere and encourage the consideration of surgical treatment in patients with focal FCD1. Neuropediatrics

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Abbreviations: FCD1, focal cortical dysplasia type I; MD, mental deficiency; learning diff, specific learning difficulty; SD, standard deviation.

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Etiology and Long-Term Outcomes of Late-Onset Infantile Spasms.

The purpose of the study was to evaluate the etiology and long-term outcomes of late-onset epileptic spasms (LOS)...
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