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Postoperative development of children after hemispherotomy
Brain & Development 24 (2002) 155–160 www.elsevier.com/locate/braindev
Original article
Postoperative development of children after hemispherotomy Taketoshi Maehara a,*, Hiroyuki Shimizu a, Kensuke Kawai a, Ritsuko Shigetomo b, Kimiko Tamagawa b, Toshitaka Yamada c, Mari Inoue c a
Department of Neurosurgery, Tokyo Metropolitan Neurological Hospital, 2-6-1 Musashidai, Fuchu-shi, Tokyo 183-0042, Japan b Department of Neuropediatrics, Tokyo Metropolitan Neurological Hospital, Fuchu, Tokyo, Japan c Department of Neuropsychiatry, Tokyo Metropolitan Neurological Hospital, Fuchu, Tokyo, Japan Received 13 August 2001; received in revised form 4 December 2001; accepted 25 December 2001
Abstract We studied the postoperative development of 14 children with cortical dysgenesis who underwent modified functional hemispherectomy (hemispherotomy) at the age of 6 years or younger. At follow-up of 24–72 months (median of 47 months), six (43%) were seizure-free, six achieved . 90% reduction, one achieved 50–90% reduction, and one achieved 0–50% reduction in seizure frequency. At the preoperative and final postoperative examinations, mean scores of developmental quotient (DQ) were as follows: 25.5 and 31.9 in total DQ, 26.0 and 33.7 in intellectual DQ, and 27.4 and 22.9 in motor DQ. Children scoring . 50 points in preoperative intellectual DQ score obtained near-normal intellectual DQ postoperatively, while, those scoring , 10 DQ preoperatively remained at a low developmental level. Among children with DQ scores in the range from 10 to 50, two children who obtained seizure-free outcome and were operated upon in the first 3 years of life achieved marked developmental progress. The present study indicated that high preoperative intellectual DQ and cessation of seizures seem to be associated with better postoperative intellectual development. However, long-term observation of postoperative development and an accumulation of more cases will be needed before we can reach a firm conclusion. q 2002 Elsevier Science B.V. All rights reserved. Keywords: Hemispherectomy; Hemimegalencephaly; Focal cortical dysplasia; Development; Children
1. Introduction Cortical dysgenesis has recently been recognized as an important pathology of children with medically refractory epilepsy [1]. As their epilepsy is often catastrophic due to the frequency and intractability of the seizures, hemispherectomy is applied to selected children, most often to infants with hemimegalencephaly (HME) [2–4]. However, in assessing benefits for the developmental process in these children, seizure control alone is not the best measure of the effectiveness of epilepsy surgery [5,6] since the children inevitably have a combination of mental retardation and motor dysfunction. For adequate measurement of the success of hemispherectomy, postoperative assessments of intellectual development and motor function are mandatory [4,7]. In this study we examined the postoperative development of hemispherectomized children with cortical dysgenesis, * Corresponding author. Neurosurgery, Department of Brain Medical Science, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan. Tel.: 181-3-5803-5266; fax: 1813-5803-0140. E-mail address: [email protected] (T. Maehara).
focusing on factors associated with better intellectual development.
2. Methods 2.1. Patients Between October 1994 and March 1998, we performed a modified functional hemispherectomy (hemispherotomy) on 15 children aged 6 years or less who had intractable epilepsy caused by cortical dysgenesis. We employed a modified version [8] of the peri-insular hemispherotomy reported by Villemure [9]. One child became severely disabled due to acute brain swelling and was excluded from the study, so, our final series consisted of 14 children (six left and eight right sides). All of the children were followed up for at least 2 years after surgery. The patients consisted of eight males and six females, ranging in age from 4 months to 6 years 5 months, with a median age of 2 years 5 months. Five infants were operated on in the first year of life. The age at seizure onset ranged from birth to 20 months, with a median of 2 months.
0387-7604/02/$ - see front matter q 2002 Elsevier Science B.V. All rights reserved. PII: S 0387-760 4(02)00010-4
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T. Maehara et al. / Brain & Development 24 (2002) 155–160
2.2. Presurgical evaluation
3. Results
All patients were referred to our hospital from pediatric epilepsy centers after medical treatments and preoperative examinations. All of them underwent repeated scalp EEGs and continuous video-EEG monitoring at our hospital to detect epileptogenic areas. All patients underwent a single photon emission computed tomography (SPECT) study and magnetic resonance imaging (MRI) with a 0.5-T (n ¼ 5) or 1.5-T (n ¼ 9) magnet. Neuropediatricians checked the neurological abnormalities of the patients and a rehabilitation specialist examined their motor function. Neuropsychologists assessed the patients’ development using the Kyoto Scale of Psychological Development [10,11]. This test consists of 324 items covering postural -motor, cognitive-adaptive, and personalsocial areas. The developmental performance of the children is expressed as the developmental age (DA) for each behavior area and for all three areas combined. We evaluated total, intellectual (the mean of cognitive-adaptive and personal-social), and motor (postural-motor) DA in the present study. As a common measure of child development, we used the developmental quotient (DQ), a score calculated by dividing the estimated DA by the chronological age and then multiplying 100.
3.1. General information
2.3. Patient selection Infants and young children with cortical dysgenesis were selected for surgery when they had intractable seizures that were resistant to appropriate trials of multiple antiepileptic drugs. Hemispherectomy was applied to patients when the intractable seizures seemed to be unilateral based upon seizure patterns and findings of MRI, interictal EEG, ictal EEG, and SPECT. A hemiparesis contralateral to the affected hemisphere was not mandatory. Infants with spasm-like seizures were considered candidates for hemispherectomy when the epileptic discharges were confined to an affected hemisphere or synchronized in both hemispheres. 2.4. Postoperative follow-up Postoperative seizures were assessed at 6 months, and at least once every year after the operation through follow-up admissions, and outpatient visits, or telephone and mail contacts. Most of the children also underwent developmental evaluation during these assessments. We analyzed the factors influencing postoperative intellectual development, particularly preoperative development and seizure outcome. When the children were admitted at 6 months and at 1 year, all of them underwent MRI in three planes to detect incomplete disconnection of the affected hemisphere, and also scalp EEGs to examine the epileptogenicity of the unaffected hemisphere.
Table 1 shows characteristics of 14 children who underwent hemispherectomy. MRI demonstrated eight holohemispheric HMEs, five focal cortical dysplasias (FCDs), and one polymicrogyria (PMG), all of which were subsequently confirmed by pathological examination. In one child with FCD, dysplastic areas were observed throughout an entire hemisphere. In one child with PMG and two children with FCD, the frontal, temporal, and parietal lobes were affected. In the remaining two children with FCD, dysplastic areas were found in the frontal and parietal lobes, and epileptic discharges were most active in the temporal and occipital lobes. Interictal SPECT was obtained in seven children, and ictal or peri-ictal SPECT was obtained in seven children. Abnormal regional cerebral blood flow in the affected hemisphere was observed in 12 children. Seizures in 13 children were predominantly unilateral during the course of the illness, but they were frequently generalized or resembled infantile spasms. Just before the operation, two children presented with status epilepticus necessitating intubation, three suffered from epilepsia partialis continua, and six had daily generalized seizures. Interictal epileptiform discharges were detected in all 14 children, appearing unilaterally in three cases and bilaterally in 11 cases. Ictal recordings were available in ten children, and the recordings were unilateral in four of the children. None of the children showed ictal onset in the opposite healthy hemisphere. Ventriculo-peritoneal shunts were placed in one HME child with high-pressure hydrocephalus and two HME children with normal-pressure hydrocephalus. One HME child underwent an additional partial callosotomy to disconnect an incompletely resected corpus callosum. Patients were followed up for 24–72 months after hemispherotomy, with a median follow-up time of 47 months. 3.2. Seizure outcome Six (43%) children were seizure-free, six achieved . 90% reduction in seizure frequency, one achieved 50– 90% seizure reduction, and one achieved 0–50% seizure reduction. In the patients who failed to obtain a seizurefree outcome, the residual seizures were partial seizures that were hardly generalized and never lasted more than a few minutes. Among the six seizure-free children, three were taken off anti-epileptic drugs within 6 months after the surgery. The other three patients with a seizure-free outcome are still being treated with antiepileptic drugs as their postoperative EEGs continue to demonstrate epileptic discharges in the unaffected hemisphere. 3.3. Developmental outcome Table 2 shows the mean of the preoperative evaluation
Table 1 Characteristics of patients a Age at seizure Seizure type onset
Pre- and (post-) operative seizure frequency
Interictal EEG abnormality MRI findings/dysplastic Follow-up period lobes (months)
Seizure outcome
1/F/8
20 days
Status epilepticus (free)
Unilateral
CD/F,T,P
29
Free
2/F/65
20 months
Several/day (free)
Bilateral synchronous
PMG/F,T,P
65
Free
10/day (free)
Bilateral independent
CD/hemispheric
54
Free without drug
Several/day (free)
Bilateral synchronous
HME/hemispheric
40
Free
EPC (free)
Bilateral synchronous
HME/hemispheric
72
Free without drug
20/day (free)
Unilateral
HME/hemispheric
62
Free without drug
10/day (several/week)
Bilateral independent
CD/F,P
39
.90% reduction
20/day (10–20/day)
Bilateral independent
CD/F,T,P
24
0–50% reduction
10/day (several/day)
Bilateral synchronous
HMC/hemispheric
45
50–90% reduction
20/day (1–2/day) 10/day (several/week)
Bilateral synchronous Unilateral
HMC/hemispheric CD/F,P
44 61
.90% reduction .90% reduction
status epilepticus (several/ day) EPC (several/day)
Bilateral synchronous
HMC/hemispheric
28
.90% reduction
Bilateral independent
HMC/hemispheric
46
.90% reduction
EPC (several/day)
Bilateral independent
HMC/hemispheric
55
.90% reduction
3/M/34
0 days
4/M/8
44 days
5/M/19
3 days
6/M/14
3 days
7/M/4
0 days
8/M/10
26 days
9/F/14
4 days
10/M/59 11/M/77
1 day 75 days
12/M/10
40 days
13/F/39
0 days
14/F/38
0 days
SPS secondary generalized SPS secondary generalized SPS secondary generalized SPS secondary generalized (temporary remission) SPS secondary generalized SPS secondary generalized SPS CPS secondary generalized SPS secondary generalized SPS secondary generalized (temporary remission) SPS CPS SPS CPS secondary generalized SPS secondary generalized SPS secondary generalized SPS secondary generalized
T. Maehara et al. / Brain & Development 24 (2002) 155–160
No./sex/age at operation (months)
a MRI, magnetic resonance imaging; SPS, simple partial seizures; CPS, complex partial seizures; EPC, epilepsia partialis continua; CD, cortical dysplasia; PMG, polymicrogyria; HMC, hemimegalencephaly; F, frontal; T, temporal; P, parietal.
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Table 2 Mean of pre- and postoperative development a Time at examination (mean chronological age)
Preoperative (28.5 months)
Postoperative (75 months)
Total DA Total DQ Intellectual DA Intellectual DQ Motor DA Motor DQ
7.4 months 25.5 7.1 months 26.0 7.9 months 27.4
21.4 months 31.9 25.0 months 33.7 18.4 months 22.9
a
DA, developmental age; DQ, developmental quotient.
and latest evaluation of postoperative development. In the assessments of postoperative DA, the children’s intellectual and motor function both progressed. While the total and intellectual DQ scores both improved postoperatively, the motor DQ score remained slightly impaired. All three of the children who had spoken preoperatively showed improved speech function, and seven of the remaining 11 children who had not spoken gained the ability to speak at least a single word. Apparent hemiparesis was observed before hemispherotomy in 12 patients, and a decrease in spontaneous movement of the hand on the side opposite the affected hemisphere was noticed in two infants. After the procedure, all of the children had hemiparesis characterized by absence of elaborate individual finger movements with preservation of shoulder, elbow, and some finger flexion. The three children who had walked preoperatively regained ambulation within 1 month after the operation. Among the remaining 11 children who had been nonambulatory, four children were able to walk after the procedure. 3.4. Factors influencing intellectual function Among the six children who obtained seizure-free outcome, four children showed good developmental progress (Fig. 1). On the other hand, all eight children with residual seizures showed slow developmental progress,
Fig. 1. Pre- and postoperative intellectual developmental quotient of hemispherectomized children with seizure-free outcome.
and their postoperative DQ was almost unchanged from their preoperative DQ (Fig. 1). Group A children (preoperative intellectual DQ score .50 points) gained near-normal intellectual DQ postoperatively, group B children (preoperative intellectual DQ score ¼ 10–50 points) showed slight postoperative DQ improvement, and group C children ð,10 points of preoperative intellectual DQ score) remained at an extremely low developmental level (Table 3). The group A children (one cortical dysplasia and one polymicrogyria) obtained seizure-free outcome after hemispherotomy (Fig. 1). While group C children (three HMEs) achieved dramatic seizure reduction, they still have postoperative seizures (Fig. 2). Among group B children, five children with residual seizures showed almost the same DQ after surgery (Fig. 2). On the other hand, two children with seizure-free outcome showed marked improvement in postoperative intellectual DQ. These two children were operated upon in the first 3 years of life (Fig. 1).
4. Discussion In the present series of hemispherotomies, we examined total, intellectual, and motor development after surgery. Our results indicated that worthwhile seizure reduction following hemispherotomy effectively facilitates the steady development of children with cortical dysgenesis, especially the development of intellectual function. Numerous recent reports have confirmed that functional hemispherectomy can assure steady postoperative development in children by reducing their seizures [2,6,12–15]. In our series of children with moderately or severely delayed development, almost all of patients obtained good seizure outcome and postoperative intellectual development. Even in the children with residual seizures, their postoperative DQ was almost the same as the preoperative DQ. The dramatic seizure reduction both in frequency and severity seems to be associated with a constant postoperative intellectual development. Wyllie et al. indicated that surgical intervention usually assures postoperative development in infants who attain not only Engel Class I [16], but also Class II or III outcome [12]. Taha et al. reported that three children with HME who underwent hemispherectomy achieved constant postoperative development, while another two children with HME treated medically showed a gradual decrease in the rate of development, with one ultimately dying of status epilepticus [2]. In infants with catastrophic epilepsy, transient development observed in the seizure-free period soon disappears or deteriorates with the resumption of intractable seizures [5], and in the absence of effective treatment patients eventually show severely delayed development [17]. While steady developmental progress of intellectual function can be obtained in hemispherectomized children, motor
T. Maehara et al. / Brain & Development 24 (2002) 155–160
159
Table 3 Pre- and postoperative intellectual DQ Group
A B C
Preoperative intellectual DQ
.50 10–50 ,10
No. of patients
Mean of intellectual DQ
2 9 3
dysfunction is one of the inevitable burdens of illness in hemispherectomized children with catastrophic epilepsy [4,18]. In the present series of infants and young children, all of the children had improved motor DA after hemispherotomy. While malfunctioning of the unilateral hand was a main cause of low motor DQ, postoperative motor functions were not impaired, and rather than suffering new burdens in their daily life, they gained an improved quality of life through satisfactory seizure control [19]. The sacrifice of the motor strip after hemispherotomy will not add a substantial burden in developmentally delayed children with cortical dysgenesis [4]. In addition to overall development following hemispherotomy, we further investigated factors influencing intellectual development. The present study showed that four out of 14 children showed a better intellectual progress after surgery. Although a statistical analysis is difficult due to the small number of subjects, we found that postoperative cessation of seizures and a high intellectual DQ before surgery seem to be associated with a better intellectual development. Previous studies reported that a high level of preoperative development is a good prognostic factor of postoperative development [13,19]. Battaglia et al. reported that two children with normal and moderately delayed development showed a better mental outcome and improved language function following hemispherectomy [19]. However, infants with severe developmental delays due to hemimegalencephaly did not show postoperative cognitive progress [5,19]. Asarnow et al. statistically confirmed that the presurgical
Preoperative
Postoperative
63.6 25.2 3.2
84.7 32.4 3.5
developmental level is important for postoperative development [13]. A preoperative developmental assessment is required to predict the approximate developmental outcome after hemispherectomy [15]. As for seizure outcome, complete disappearance of seizures was suggested to be an indispensable condition for the better postoperative development [19] since a seizure-free outcome means little or no epileptogenicity in the unaffected hemisphere. Given the high frequency with which bilateral interictal EEG abnormality [4,20] and bilateral neuropathologic changes [21] are found in children with developmental lesions, we can conclude that the remaining seizures are derived from the opposite healthy hemisphere. Rintahaka et al. reported that HME children had a relatively poor overall developmental outcome due to dysfunction in the structurally ‘normal’ non-HME hemisphere [22]. Normal function of the healthy hemisphere is required to achieve favorable intellectual development [13,22]. We also noticed marked developmental progress in two children who underwent hemispherectomy at the age of 2 years or less. Several papers recommended that early surgery is more likely to achieve a better developmental outcome since early intervention benefits from maximum plasticity of the opposite healthy brain [6,13]. However, there is a counterargument to ‘the-earlier-the better’ hypothesis following hemispherectomy [23]. Long-term observation of postoperative development and the accumulation of more cases will be needed before we can reach a conclusion.
Acknowledgements This work was supported by the Japan Epilepsy Research Foundation (1996).
References
Fig. 2. Pre- and postoperative intellectual developmental quotient of hemispherectomized children with residual seizures.
[1] Palmini A, Andermann F, Olivier A, Tampieri D, Robitaille Y, Andermann E, et al. Focal neuronal migration disorders and intractable partial epilepsy: a study of 30 patients. Ann Neurol 1991;30:741– 749. [2] Taha JM, Crone KR, Berger TS. The role of hemispherectomy in the treatment of holohemispheric hemimegalencephaly. J Neurosurg 1994;81:37–42. [3] Vigevano F, Bertini E, Boldrini R, Bosman C, Claps D, di Capua M, et al. Hemimegalencephaly and intractable epilepsy: benefits of hemispherectomy. Epilepsia 1989;30:833–843.
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[4] Vining EPG, Freeman JM, Pillas DJ, Uematsu S, Carson BS, Brandt J, et al. Why would you remove half a brain? The outcome of 58 children after hemispherectomy – The Johns Hopkins Experience: 1968 to 1996. Pediatrics 1997;100:163–171. [5] Wyllie E. Surgery for catastrophic localization-related epilepsy in infants. Epilepsia 1996;37(Suppl 1):22–25. [6] Duchowny M, Jayakar P, Resnick T, Harvey AS, Alvarez L, Dean P, et al. Epilepsy surgery in the first three years of life. Epilepsia 1998;39:737–743. [7] Maehara T, Shimizh H, Shigetomo R, Tamagawa K. Functional hemispherectomy for children aged 2 years or less for the treatment of intractable epilepsy caused by cortical dysgenesis (in Japanese). No To Hattatsu (Tokyo) 2000;32:335–340. [8] Shimizu H, Maehara T. Modification of peri-insular hemispherotomy and its surgical results. Neurosurgery 2000;47:357–373. [9] Villemur JG, Mascott C. Peri-insular hemispherotomy: surgical principles and anatomy. Neurosurgery 1995;37:975–981. [10] Ikuzawa M. A latent class analysis of the Kyoto Scale of Psychological Development. In: Wilpert B, Motoaki H, Misumi J, editors. Proceedings of the 22nd international congress of applied psychology, vol. 2. Hillsdale, NJ: Lawrence Erlbaum, 1990. pp. 288–289. [11] Ikuzawa M, Matsushita Y, Nakase A. The Kyoto Scale of Psychological Development. 2nd ed. Kyoto: Nakanishiya Publishers, 1995 in Japanese. [12] Wyllie E, Comair YG, Kotagal P, Raja S, Ruggieri P. Epilepsy surgery in infants. Epilepsia 1996;37:625–637. [13] Asarnow RF, Lopresti C, Guthrie D, Elliott T, Cynn V, Shields WD, et al. Developmental outcomes in children receiving resection surgery for medically intractable infantile spasms. Dev Med Child Neurol 1997;39:430–440. [14] Chugani HT, Shields WD, Shewmon DA, Olson DM, Phelps ME,
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Original article
Postoperative development of children after hemispherotomy Taketoshi Maehara a,*, Hiroyuki Shimizu a, Kensuke Kawai a, Ritsuko Shigetomo b, Kimiko Tamagawa b, Toshitaka Yamada c, Mari Inoue c a
Department of Neurosurgery, Tokyo Metropolitan Neurological Hospital, 2-6-1 Musashidai, Fuchu-shi, Tokyo 183-0042, Japan b Department of Neuropediatrics, Tokyo Metropolitan Neurological Hospital, Fuchu, Tokyo, Japan c Department of Neuropsychiatry, Tokyo Metropolitan Neurological Hospital, Fuchu, Tokyo, Japan Received 13 August 2001; received in revised form 4 December 2001; accepted 25 December 2001
Abstract We studied the postoperative development of 14 children with cortical dysgenesis who underwent modified functional hemispherectomy (hemispherotomy) at the age of 6 years or younger. At follow-up of 24–72 months (median of 47 months), six (43%) were seizure-free, six achieved . 90% reduction, one achieved 50–90% reduction, and one achieved 0–50% reduction in seizure frequency. At the preoperative and final postoperative examinations, mean scores of developmental quotient (DQ) were as follows: 25.5 and 31.9 in total DQ, 26.0 and 33.7 in intellectual DQ, and 27.4 and 22.9 in motor DQ. Children scoring . 50 points in preoperative intellectual DQ score obtained near-normal intellectual DQ postoperatively, while, those scoring , 10 DQ preoperatively remained at a low developmental level. Among children with DQ scores in the range from 10 to 50, two children who obtained seizure-free outcome and were operated upon in the first 3 years of life achieved marked developmental progress. The present study indicated that high preoperative intellectual DQ and cessation of seizures seem to be associated with better postoperative intellectual development. However, long-term observation of postoperative development and an accumulation of more cases will be needed before we can reach a firm conclusion. q 2002 Elsevier Science B.V. All rights reserved. Keywords: Hemispherectomy; Hemimegalencephaly; Focal cortical dysplasia; Development; Children
1. Introduction Cortical dysgenesis has recently been recognized as an important pathology of children with medically refractory epilepsy [1]. As their epilepsy is often catastrophic due to the frequency and intractability of the seizures, hemispherectomy is applied to selected children, most often to infants with hemimegalencephaly (HME) [2–4]. However, in assessing benefits for the developmental process in these children, seizure control alone is not the best measure of the effectiveness of epilepsy surgery [5,6] since the children inevitably have a combination of mental retardation and motor dysfunction. For adequate measurement of the success of hemispherectomy, postoperative assessments of intellectual development and motor function are mandatory [4,7]. In this study we examined the postoperative development of hemispherectomized children with cortical dysgenesis, * Corresponding author. Neurosurgery, Department of Brain Medical Science, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan. Tel.: 181-3-5803-5266; fax: 1813-5803-0140. E-mail address: [email protected] (T. Maehara).
focusing on factors associated with better intellectual development.
2. Methods 2.1. Patients Between October 1994 and March 1998, we performed a modified functional hemispherectomy (hemispherotomy) on 15 children aged 6 years or less who had intractable epilepsy caused by cortical dysgenesis. We employed a modified version [8] of the peri-insular hemispherotomy reported by Villemure [9]. One child became severely disabled due to acute brain swelling and was excluded from the study, so, our final series consisted of 14 children (six left and eight right sides). All of the children were followed up for at least 2 years after surgery. The patients consisted of eight males and six females, ranging in age from 4 months to 6 years 5 months, with a median age of 2 years 5 months. Five infants were operated on in the first year of life. The age at seizure onset ranged from birth to 20 months, with a median of 2 months.
0387-7604/02/$ - see front matter q 2002 Elsevier Science B.V. All rights reserved. PII: S 0387-760 4(02)00010-4
156
T. Maehara et al. / Brain & Development 24 (2002) 155–160
2.2. Presurgical evaluation
3. Results
All patients were referred to our hospital from pediatric epilepsy centers after medical treatments and preoperative examinations. All of them underwent repeated scalp EEGs and continuous video-EEG monitoring at our hospital to detect epileptogenic areas. All patients underwent a single photon emission computed tomography (SPECT) study and magnetic resonance imaging (MRI) with a 0.5-T (n ¼ 5) or 1.5-T (n ¼ 9) magnet. Neuropediatricians checked the neurological abnormalities of the patients and a rehabilitation specialist examined their motor function. Neuropsychologists assessed the patients’ development using the Kyoto Scale of Psychological Development [10,11]. This test consists of 324 items covering postural -motor, cognitive-adaptive, and personalsocial areas. The developmental performance of the children is expressed as the developmental age (DA) for each behavior area and for all three areas combined. We evaluated total, intellectual (the mean of cognitive-adaptive and personal-social), and motor (postural-motor) DA in the present study. As a common measure of child development, we used the developmental quotient (DQ), a score calculated by dividing the estimated DA by the chronological age and then multiplying 100.
3.1. General information
2.3. Patient selection Infants and young children with cortical dysgenesis were selected for surgery when they had intractable seizures that were resistant to appropriate trials of multiple antiepileptic drugs. Hemispherectomy was applied to patients when the intractable seizures seemed to be unilateral based upon seizure patterns and findings of MRI, interictal EEG, ictal EEG, and SPECT. A hemiparesis contralateral to the affected hemisphere was not mandatory. Infants with spasm-like seizures were considered candidates for hemispherectomy when the epileptic discharges were confined to an affected hemisphere or synchronized in both hemispheres. 2.4. Postoperative follow-up Postoperative seizures were assessed at 6 months, and at least once every year after the operation through follow-up admissions, and outpatient visits, or telephone and mail contacts. Most of the children also underwent developmental evaluation during these assessments. We analyzed the factors influencing postoperative intellectual development, particularly preoperative development and seizure outcome. When the children were admitted at 6 months and at 1 year, all of them underwent MRI in three planes to detect incomplete disconnection of the affected hemisphere, and also scalp EEGs to examine the epileptogenicity of the unaffected hemisphere.
Table 1 shows characteristics of 14 children who underwent hemispherectomy. MRI demonstrated eight holohemispheric HMEs, five focal cortical dysplasias (FCDs), and one polymicrogyria (PMG), all of which were subsequently confirmed by pathological examination. In one child with FCD, dysplastic areas were observed throughout an entire hemisphere. In one child with PMG and two children with FCD, the frontal, temporal, and parietal lobes were affected. In the remaining two children with FCD, dysplastic areas were found in the frontal and parietal lobes, and epileptic discharges were most active in the temporal and occipital lobes. Interictal SPECT was obtained in seven children, and ictal or peri-ictal SPECT was obtained in seven children. Abnormal regional cerebral blood flow in the affected hemisphere was observed in 12 children. Seizures in 13 children were predominantly unilateral during the course of the illness, but they were frequently generalized or resembled infantile spasms. Just before the operation, two children presented with status epilepticus necessitating intubation, three suffered from epilepsia partialis continua, and six had daily generalized seizures. Interictal epileptiform discharges were detected in all 14 children, appearing unilaterally in three cases and bilaterally in 11 cases. Ictal recordings were available in ten children, and the recordings were unilateral in four of the children. None of the children showed ictal onset in the opposite healthy hemisphere. Ventriculo-peritoneal shunts were placed in one HME child with high-pressure hydrocephalus and two HME children with normal-pressure hydrocephalus. One HME child underwent an additional partial callosotomy to disconnect an incompletely resected corpus callosum. Patients were followed up for 24–72 months after hemispherotomy, with a median follow-up time of 47 months. 3.2. Seizure outcome Six (43%) children were seizure-free, six achieved . 90% reduction in seizure frequency, one achieved 50– 90% seizure reduction, and one achieved 0–50% seizure reduction. In the patients who failed to obtain a seizurefree outcome, the residual seizures were partial seizures that were hardly generalized and never lasted more than a few minutes. Among the six seizure-free children, three were taken off anti-epileptic drugs within 6 months after the surgery. The other three patients with a seizure-free outcome are still being treated with antiepileptic drugs as their postoperative EEGs continue to demonstrate epileptic discharges in the unaffected hemisphere. 3.3. Developmental outcome Table 2 shows the mean of the preoperative evaluation
Table 1 Characteristics of patients a Age at seizure Seizure type onset
Pre- and (post-) operative seizure frequency
Interictal EEG abnormality MRI findings/dysplastic Follow-up period lobes (months)
Seizure outcome
1/F/8
20 days
Status epilepticus (free)
Unilateral
CD/F,T,P
29
Free
2/F/65
20 months
Several/day (free)
Bilateral synchronous
PMG/F,T,P
65
Free
10/day (free)
Bilateral independent
CD/hemispheric
54
Free without drug
Several/day (free)
Bilateral synchronous
HME/hemispheric
40
Free
EPC (free)
Bilateral synchronous
HME/hemispheric
72
Free without drug
20/day (free)
Unilateral
HME/hemispheric
62
Free without drug
10/day (several/week)
Bilateral independent
CD/F,P
39
.90% reduction
20/day (10–20/day)
Bilateral independent
CD/F,T,P
24
0–50% reduction
10/day (several/day)
Bilateral synchronous
HMC/hemispheric
45
50–90% reduction
20/day (1–2/day) 10/day (several/week)
Bilateral synchronous Unilateral
HMC/hemispheric CD/F,P
44 61
.90% reduction .90% reduction
status epilepticus (several/ day) EPC (several/day)
Bilateral synchronous
HMC/hemispheric
28
.90% reduction
Bilateral independent
HMC/hemispheric
46
.90% reduction
EPC (several/day)
Bilateral independent
HMC/hemispheric
55
.90% reduction
3/M/34
0 days
4/M/8
44 days
5/M/19
3 days
6/M/14
3 days
7/M/4
0 days
8/M/10
26 days
9/F/14
4 days
10/M/59 11/M/77
1 day 75 days
12/M/10
40 days
13/F/39
0 days
14/F/38
0 days
SPS secondary generalized SPS secondary generalized SPS secondary generalized SPS secondary generalized (temporary remission) SPS secondary generalized SPS secondary generalized SPS CPS secondary generalized SPS secondary generalized SPS secondary generalized (temporary remission) SPS CPS SPS CPS secondary generalized SPS secondary generalized SPS secondary generalized SPS secondary generalized
T. Maehara et al. / Brain & Development 24 (2002) 155–160
No./sex/age at operation (months)
a MRI, magnetic resonance imaging; SPS, simple partial seizures; CPS, complex partial seizures; EPC, epilepsia partialis continua; CD, cortical dysplasia; PMG, polymicrogyria; HMC, hemimegalencephaly; F, frontal; T, temporal; P, parietal.
157
158
T. Maehara et al. / Brain & Development 24 (2002) 155–160
Table 2 Mean of pre- and postoperative development a Time at examination (mean chronological age)
Preoperative (28.5 months)
Postoperative (75 months)
Total DA Total DQ Intellectual DA Intellectual DQ Motor DA Motor DQ
7.4 months 25.5 7.1 months 26.0 7.9 months 27.4
21.4 months 31.9 25.0 months 33.7 18.4 months 22.9
a
DA, developmental age; DQ, developmental quotient.
and latest evaluation of postoperative development. In the assessments of postoperative DA, the children’s intellectual and motor function both progressed. While the total and intellectual DQ scores both improved postoperatively, the motor DQ score remained slightly impaired. All three of the children who had spoken preoperatively showed improved speech function, and seven of the remaining 11 children who had not spoken gained the ability to speak at least a single word. Apparent hemiparesis was observed before hemispherotomy in 12 patients, and a decrease in spontaneous movement of the hand on the side opposite the affected hemisphere was noticed in two infants. After the procedure, all of the children had hemiparesis characterized by absence of elaborate individual finger movements with preservation of shoulder, elbow, and some finger flexion. The three children who had walked preoperatively regained ambulation within 1 month after the operation. Among the remaining 11 children who had been nonambulatory, four children were able to walk after the procedure. 3.4. Factors influencing intellectual function Among the six children who obtained seizure-free outcome, four children showed good developmental progress (Fig. 1). On the other hand, all eight children with residual seizures showed slow developmental progress,
Fig. 1. Pre- and postoperative intellectual developmental quotient of hemispherectomized children with seizure-free outcome.
and their postoperative DQ was almost unchanged from their preoperative DQ (Fig. 1). Group A children (preoperative intellectual DQ score .50 points) gained near-normal intellectual DQ postoperatively, group B children (preoperative intellectual DQ score ¼ 10–50 points) showed slight postoperative DQ improvement, and group C children ð,10 points of preoperative intellectual DQ score) remained at an extremely low developmental level (Table 3). The group A children (one cortical dysplasia and one polymicrogyria) obtained seizure-free outcome after hemispherotomy (Fig. 1). While group C children (three HMEs) achieved dramatic seizure reduction, they still have postoperative seizures (Fig. 2). Among group B children, five children with residual seizures showed almost the same DQ after surgery (Fig. 2). On the other hand, two children with seizure-free outcome showed marked improvement in postoperative intellectual DQ. These two children were operated upon in the first 3 years of life (Fig. 1).
4. Discussion In the present series of hemispherotomies, we examined total, intellectual, and motor development after surgery. Our results indicated that worthwhile seizure reduction following hemispherotomy effectively facilitates the steady development of children with cortical dysgenesis, especially the development of intellectual function. Numerous recent reports have confirmed that functional hemispherectomy can assure steady postoperative development in children by reducing their seizures [2,6,12–15]. In our series of children with moderately or severely delayed development, almost all of patients obtained good seizure outcome and postoperative intellectual development. Even in the children with residual seizures, their postoperative DQ was almost the same as the preoperative DQ. The dramatic seizure reduction both in frequency and severity seems to be associated with a constant postoperative intellectual development. Wyllie et al. indicated that surgical intervention usually assures postoperative development in infants who attain not only Engel Class I [16], but also Class II or III outcome [12]. Taha et al. reported that three children with HME who underwent hemispherectomy achieved constant postoperative development, while another two children with HME treated medically showed a gradual decrease in the rate of development, with one ultimately dying of status epilepticus [2]. In infants with catastrophic epilepsy, transient development observed in the seizure-free period soon disappears or deteriorates with the resumption of intractable seizures [5], and in the absence of effective treatment patients eventually show severely delayed development [17]. While steady developmental progress of intellectual function can be obtained in hemispherectomized children, motor
T. Maehara et al. / Brain & Development 24 (2002) 155–160
159
Table 3 Pre- and postoperative intellectual DQ Group
A B C
Preoperative intellectual DQ
.50 10–50 ,10
No. of patients
Mean of intellectual DQ
2 9 3
dysfunction is one of the inevitable burdens of illness in hemispherectomized children with catastrophic epilepsy [4,18]. In the present series of infants and young children, all of the children had improved motor DA after hemispherotomy. While malfunctioning of the unilateral hand was a main cause of low motor DQ, postoperative motor functions were not impaired, and rather than suffering new burdens in their daily life, they gained an improved quality of life through satisfactory seizure control [19]. The sacrifice of the motor strip after hemispherotomy will not add a substantial burden in developmentally delayed children with cortical dysgenesis [4]. In addition to overall development following hemispherotomy, we further investigated factors influencing intellectual development. The present study showed that four out of 14 children showed a better intellectual progress after surgery. Although a statistical analysis is difficult due to the small number of subjects, we found that postoperative cessation of seizures and a high intellectual DQ before surgery seem to be associated with a better intellectual development. Previous studies reported that a high level of preoperative development is a good prognostic factor of postoperative development [13,19]. Battaglia et al. reported that two children with normal and moderately delayed development showed a better mental outcome and improved language function following hemispherectomy [19]. However, infants with severe developmental delays due to hemimegalencephaly did not show postoperative cognitive progress [5,19]. Asarnow et al. statistically confirmed that the presurgical
Preoperative
Postoperative
63.6 25.2 3.2
84.7 32.4 3.5
developmental level is important for postoperative development [13]. A preoperative developmental assessment is required to predict the approximate developmental outcome after hemispherectomy [15]. As for seizure outcome, complete disappearance of seizures was suggested to be an indispensable condition for the better postoperative development [19] since a seizure-free outcome means little or no epileptogenicity in the unaffected hemisphere. Given the high frequency with which bilateral interictal EEG abnormality [4,20] and bilateral neuropathologic changes [21] are found in children with developmental lesions, we can conclude that the remaining seizures are derived from the opposite healthy hemisphere. Rintahaka et al. reported that HME children had a relatively poor overall developmental outcome due to dysfunction in the structurally ‘normal’ non-HME hemisphere [22]. Normal function of the healthy hemisphere is required to achieve favorable intellectual development [13,22]. We also noticed marked developmental progress in two children who underwent hemispherectomy at the age of 2 years or less. Several papers recommended that early surgery is more likely to achieve a better developmental outcome since early intervention benefits from maximum plasticity of the opposite healthy brain [6,13]. However, there is a counterargument to ‘the-earlier-the better’ hypothesis following hemispherectomy [23]. Long-term observation of postoperative development and the accumulation of more cases will be needed before we can reach a conclusion.
Acknowledgements This work was supported by the Japan Epilepsy Research Foundation (1996).
References
Fig. 2. Pre- and postoperative intellectual developmental quotient of hemispherectomized children with residual seizures.
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