Surgical treatment of epilepsy in Sturge Weber syndrome in children

Transcription

1 J Neurosurg (1 Suppl Pediatrics) 106:20 28, 2007 Surgical treatment of epilepsy in Sturge Weber syndrome in children MARIE BOURGEOIS, M.D., 1 DARACH WILLIAM CRIMMINS, F.R.C.S.I., 2 RICARDO SANTOS DE OLIVEIRA, M.D., 3 ALEXIS ARZIMANOGLOU, M.D., 4 MATTHEW GARNETT, F.R.C.S., 1 THOMAS ROUJEAU, M.D., 1 FEDERICO DI ROCCO, M.D., 1 AND CHRISTIAN SAINTE-ROSE, M.D. 1 1 Service de Neurologie Pédiatrique, Hôpital Necker Enfants Malades, Paris, France; 2 Department of Neurosurgery, Leeds General Infirmary, Leeds, United Kingdom; 3 Division of Neurosurgery, Hospital of Clinics of Ribeirao Preto, University of Sao Paulo, Brazil; and 4 Service de Neuropédiatrie, Hôpital Robert Debré, Paris, France Object. The authors sought to analyze the success rate of surgery in the management of medically intractable epilepsy in children with Sturge Weber syndrome and to determine whether the extent and timing of surgery affected seizure and developmental outcomes. Methods. The authors performed a retrospective review of 27 children who underwent surgery at their institution for medically resistant epilepsy, and they examined the outcomes with regard to epilepsy control and neuropsychological development. Seventeen children (63%) experienced onset of their epilepsy when they were younger than 1 year of age. These patients were significantly more likely to have hemiparesis (p 0.001) and status epilepticus (p 0.001) and be developmentally delayed (p 0.025) than children whose epilepsy started later in life. Eight patients underwent a hemispherectomy (either anatomical or functional), and complete resolution of epilepsy was noted in all. Of the 19 patients in whom a focal resection was performed, 11 (58%) became seizure free. The 10 children in whom there was residual disease were more likely to have continuing epilepsy than the nine whose lesions were completely excised (p 0.05). Seventeen children exhibited improvement in their developmental status following surgery. This improvement was significantly affected by completeness of resection (p 0.05) and age at surgery (p 0.009). Seizure freedom per se was not affected by the timing of surgery. Conclusions. Medically intractable epilepsy in children can be treated effectively by surgery. The degree of resection or disconnection of diseased tissue, but not patient age at the time of surgery, is an important factor in achieving epilepsy control. Early surgery is more likely to improve developmental outcome. KEY WORDS Sturge Weber syndrome epilepsy surgery hemispherectomy hemispherotomy focal resection pediatric neurosurgery S TURGE WEBER syndrome is a congenital neurocutaneous condition characterized by a facial nevus in one or more divisions of the trigeminal nerve with ipsilateral leptomeningeal venous angioma. The natural history of the disease is characterized by the development of cortical calcifications and cerebral atrophy. Epilepsy is present in 80% of patients, and seizures develop in two thirds of those younger than 1 year of age. 35 Patients are clinically affected to a varying degree. Some remain seizure free and suffer no neurological deficits, Abbreviations used in this paper: CT = computed tomography; DQ = developmental quotient; EEG = electroencephalography; IQ = intelligence quotient; MR = magnetic resonance; SWS = Sturge Weber syndrome. whereas others have severe medically intractable epilepsy, profound neurological deficits, and developmental delay. 1 In the patients in whom seizures develop early (patient age 1 year), the epilepsy can be difficult to control and is associated with progressive neurological deterioration and intellectual impairment. 26,35 Authors of many studies have advocated early surgery (removal of abnormal cortex or hemispherectomy) in this group of patients to attain seizure control, prevent the progression of hemiparesis, and maximize developmental progress. 7,11,12,18,19,27,30,37 Other authors have taken a more circumspect approach and advise surgery only in those patients whose seizures are frequent and in whom an adequate period of medical treatment has been undertaken. 1,22 The purpose of this retrospective study was to determine whether early surgery had an impact on seizure control, mo- 20 J. Neurosurg: Pediatrics / Volume 106 / January, 2007

2 Epilepsy surgery in Sturge Weber syndrome tor deficits, and developmental outcome in patients with SWS. In addition, we sought to determine whether the completeness of resection influenced seizure control and developmental outcome in these patients. Patient Population Clinical Material and Methods We evaluated the cases of all children with SWS who were treated surgically between January 1978 and December 2002 at Hôpital Necker Enfants Malades. All patients had medically intractable epilepsy. In patients with focal disease, medically intractable epilepsy was defined as ongoing seizure activity despite the use of at least two major antiepileptic drugs for 6 months. In patients with diffuse disease (hemispheric or multilobar), surgery was often undertaken before the 6-month period had ended because of early resistant status epilepticus and rapid evolution toward catastrophic epilepsy associated with evolving neurodevelopmental deficits. The patients medical notes were reviewed, and their clinical data (seizure severity, presence of motor deficits, and facial angiomas), electrophysiological data, ophthalmological findings, and developmental assessments were recorded. All neuroimages were reviewed to determine the extent of the cerebral disease. The ages of the patients at seizure onset and at the time of surgery were also recorded. Presurgical Evaluation and Neuroimaging All patients underwent a thorough general physical and neurological examination. The diagnosis of SWS was established by the presence of a facial nevus flammeus and seizures. In those without any cutaneous abnormality, the diagnosis was confirmed by observing cerebral calcifications and atrophy on CT scanning or leptomeningeal angiomatosis and atrophy on Gd-enhanced MR imaging. Seizures were divided into different categories: simple partial, complex partial, simple partial plus secondarily generalized tonic clonic, complex partial plus secondarily generalized tonic clonic, and mixed simple and complex partial seizures (focal clonic or tonic with complex symptomatology, for example, unilateral motor seizures in addition to complex partial seizures). Seizure frequency was also divided into four groups: daily with an average of at least one seizure per day (and sometimes many more), weekly, monthly, and yearly or episodic seizures. Neuropsychological Testing During the follow-up period, serial neurological evaluations and developmental testing were performed. In children younger than 30 months of age, the Brunet Lezine test (DQ) was used to assess development, whereas in children 30 months or older the Weschler test (IQ) was used. Evaluations were performed every 6 months for the first 2 years of life and yearly thereafter. The DQ/IQ results were categorized into normal (either verbal or performance DQ/ IQ 90), mildly delayed (normal DQ/IQ but with learning disabilities [memory and attention deficits, slow information processing, and problem-solving difficulties]), moderately delayed (DQ/IQ 50 90), and severely delayed (DQ/ IQ 50). Behavioral and psychosocial aspects were divided into four groups: normal, psychological impairment (inhibition and obsession), hyperactivity, and psychosis. School performance was also studied, and children were grouped as follows: normal schooling, moderate difficulties with a school delay of less than 2 years, significant difficulties with a delay of greater than 2 years, those with no possibility of schooling, and those who were too young ( 6 years) for school. Assessment of EEG Studies The interictal scalp EEG study was assessed for background activity, slow waves, focal spikes, and generalized paroxysmal discharges in each child. Background activity was classified as normal, asymmetrical, or slow wave. Focal spikes were identified as localized, regional, multifocal, or hemispheric with or without focal, regional, or hemispheric slow waves. Generalized paroxysmal discharges included diffuse irregular spike-and-wave activity or multiple spikes and waves, but excluded diffuse high-voltage slow bursts. Repeated EEG was performed in all patients. Prolonged video-eeg recordings were undertaken in most patients. Surgical Procedure The indication for surgery in all cases was the presence of medically intractable epilepsy. In those with focal disease, complete excision was attempted. In patients without motor deficits, intraoperative stimulation was used in children older than 8 years of age to localize the motor cortex near the abnormal brain. Some of these children underwent a subtotal removal of the diseased area. In children with diffuse disease (extensive hemispheric angiomatosis and hemiparesis), either an anatomical hemispherectomy (performed earlier in the series) or a functional hemispherectomy (performed later in the series) was performed to disconnect the entire cortex from the underlying diencephalic structures. 38 In these cases the resection was considered complete. Postoperative Follow-Up Examinations The follow-up examinations were completed in September 2006, resulting in a minimum follow-up period of 9 months. At the end of this period, the children underwent another neurological examination including neuropsychological testing. The postoperative seizure outcome was assessed using the classification adapted from Engel. 14 Statistical Analysis Statistical analysis was performed using SPSS for Windows version 10 software (SPSS, Inc.). We compared categorical data using the chi-square test and the Fisher exact test, and the means between groups using the Student unpaired t-test. A probability value was deemed significant at less than Patient Characteristics Results A summary of preoperative patient characteristics is shown in Table 1. Twenty-seven children were included in J. Neurosurg: Pediatrics / Volume 106 / January,

3 M. Bourgeois et al. TABLE 1 Preoperative characteristics in 27 children with SWS who underwent surgery for intractable epilepsy Case Age at Seizure Status Seizure Duration No. Onset (mos) Facial Nevus Motor Deficit Developmental Delay Epilepticus (mos)* none none severe no none none severe no none none mild no unilat hemiparesis severe yes bilat hemiparesis severe yes unilat hemiplegia mild yes none none moderate yes unilat hemiparesis mild no none none none no unilat none none no none none severe no unilat none moderate no none none moderate no bilat hemiplegia severe yes unilat hemiparesis severe yes none none moderate yes none none none yes none none none no unilat hemiparesis moderate yes none none mild no none none none no unilat hemiplegia severe yes unilat hemiparesis moderate yes unilat hemiparesis moderate yes unilat hemiparesis severe yes bilat hemiparesis severe yes unilat hemiparesis severe yes 13.6 * Interval between seizure onset and surgery. the study, of whom 14 (52%) were male. A facial angioma was present in 15 children (56%); in three it was bilateral. Six children (22%) had glaucoma, and seven had a choroidal angioma. Thirteen patients (48%) exhibited some degree of hemiparesis preoperatively, and 18 (67%) had a demonstrable visual field deficit. Twenty-two patients (81%) presented with developmental delay. Of these 22, four (18%) displayed mild delay, seven (32%) moderate delay, and 11 (50%) severe delay. Eleven children were older than 6 years of age at the time of surgery. Only five of these were in mainstream school in the appropriate class for their age. Seizure Onset The median patient age at seizure onset was 9.1 months (range 1.9 months 12.3 years, mean months). Seventeen children experienced seizure onset before 1 year of age. All patients had partial seizures (mainly clonic involving one limb or side of the body) with secondary generalization occurring in 15 (56%). Fourteen children (52%) had seizures at least once a day, and 15 (56%) had suffered from status epilepticus at some stage. The mean age at seizure onset in the 15 children with a facial nevus ( months) was significantly less than in those who had no cutaneous abnormalities ( months) (p = 0.004, Student t-test). The age at onset of seizures significantly affected motor function, developmental status, and the severity of seizures. Children in whom epilepsy developed when they were younger than 1 year old were more likely to suffer hemiparesis (p 0.001), to have had an episode of status epilepticus (p 0.001), and to be developmentally delayed (p 0.025) (Table 2). The median interval from seizure onset to surgery (seizure duration) was 33.1 months (range 10 days 11.4 years, mean months). Of note, two patients underwent surgery within a month of seizure onset. One patient was admitted with intractable status epilepticus, despite a 1-week pentothal therapy regimen, and underwent surgery 26 days after the seizures began. At the beginning of the study period, the other patient underwent a partial resection 10 days after seizure onset; the preoperative diagnosis had been unclear. The duration of seizures did not significantly affect motor function, the severity of seizures, or developmental status. Neurophysiological Findings Interictal scalp EEG demonstrated abnormalities in all 27 children. The most consistent finding in the patients with diffuse disease was asymmetrical spike wave activity. In patients with focal disease, interictal EEG showed focal spikes and spike waves. Seizures were recorded in 19 of the 20 children who underwent video-eeg telemetry. In cases of diffuse hemispheric angioma, the ictal EEG tended to show diffuse unilateral spikes or theta activity, whereas in focal disease, focal spikes, low-voltage fast rhythms, and theta waves were more common. Imaging Modalities All patients underwent CT and/or MR imaging pre- and postoperatively. A CT scan was obtained in 25 children, and there was evidence of calcification in all. Eighteen children 22 J. Neurosurg: Pediatrics / Volume 106 / January, 2007

4 Epilepsy surgery in Sturge Weber syndrome TABLE 2 Effects of seizure onset and duration to surgery on presence of motor deficits, history of status epilepticus, and neuropsychological development* Developmental Status (%) Motor Deficit (%) Status Epilepticus (%) Moderate Normal No Statistical Statistical or Severe or Mild Statistical Parameter Hemiparesis Hemiparesis Value Present Absent Value Delay Delay Value seizure onset 1 yr 13 (76.5) 4 (23.5) 2 = ; 14 (82) 3 (18) 2 = ; 14 (82) 3 (18) 2 = 5.082; p p p seizure onset 1 yr 0 (0) 10 (100) 1 (10) 9 (90) 4 (40) 6 (60) seizure duration 1 yr 6 (86) 1 (14) 2 = 3.825; 6 (86) 1 (14) 2 = 2.411; 6 (86) 1 (14) 2 = 0.964; p 0.1 p 0.2 p 1.0 seizure duration 1 yr 7 (35) 13 (65) 9 (45) 11 (55) 12 (60) 8 (40) * Values represent numbers of patients unless otherwise specified. underwent Gd-enhanced MR imaging, and all were shown to have pial angioma. Focal or diffuse atrophy was present on imaging in 17 (63%) of the 27 children. At the beginning of the study, when MR imaging was unavailable, CT scanning was used preoperatively to help diagnose and localize the disease. Preoperative MR images confirming cortical angiomatosis are shown in Fig. 1A, while a typical preoperative CT scan with calcification visible in the right occipital region is shown in Fig. 1B. Intraoperatively, however, the resection margins were limited by macroscopically abnormal tissue. Postoperative CT scanning, usually performed within 2 days, allowed an approximation of the extent of resection but was primarily performed to detect possible operative complications. Figure 1C shows postoperative MR images that confirm complete resection. Currently, MR imaging is the gold standard both to plan the resection and to confirm the limits of resection postoperatively. It is clear, however, that even this modern examination may also underestimate the extent of vascular disease. Surgical Procedure Eight patients underwent a hemispherectomy, five an anatomical resection, and three functional disconnection (Fig. 2). A multilobar resection was performed in 10 patients and a focal resection in nine. The median age at the time of surgery was 9.1 months (range years, mean months). In 10 cases the resection of the pial angiomatosis was incomplete because of its proximity to eloquent cortex (motor or language areas). The operative details and outcomes are shown in Table 3. The diagnosis of SWS was confirmed by histological examination of the resected material in all cases. Seizure Outcome The median follow-up period in this series was 88.2 months (range 9 months 17.4 years, mean months). Nineteen patients remained seizure free (Engel Class Ia) following surgery and had a median follow-up period of 48 months. The degree of resection was significant in predicting seizure outcome in these children. Sixteen (94%) of the 17 patients who had undergone a complete resection or hemispherectomy remained seizure free compared with only three (30%) of the 10 who underwent partial resection of their lesion (p = 0.002). Even when we excluded the eight patients who underwent a hemispherectomy (all of whom were seizure free), those in whom complete resection was performed had a higher incidence of seizure freedom (89%) than those in whom it was not (p 0.05) (Table 4). Developmental Outcome The developmental status of all 27 children immediately before surgery and at the end of the follow-up period is shown in Tables 1 and 3. It should be noted, however, that the preoperative score was not an IQ but a developmental coefficient (DQ) in the nine children who were younger than 30 months at the time of surgery. Nine children exhibited a normal DQ or IQ at the final follow-up examination, nine a mild delay, six a moderate delay, and three children were severely handicapped. Sixteen children (59%) improved with respect to their cognitive assessment following surgery (for example, improving from a moderate to a mild delay). There was no developmental change in 10 children postoperatively, and one child s condition worsened after undergoing a difficult surgical procedure at the beginning of the series. Developmental improvement was more frequent in those who underwent complete resection or hemispherectomy than in those who underwent an incomplete resection (12 of 17 compared with four of 10, p 0.05) (Table 4) and in those who were seizure free than in those who were not (14 of 19 compared with two of eight, p 0.025). The patient age at which surgery was performed was also an important determinant of improvement in developmental status. The mean age at surgery of patients whose conditions improved was months, and in those whose did not improve the mean age was months (p = 0.009, Student t-test). There was no such correlation between the interval from seizure onset to surgery (duration of seizures) and cognitive improvement. School performance was assessed in 23 children who were 6 years or older at follow up. Six (22%) of the patients in the study were in a regular school in the appropriate class for their age. All of these children had been treated for focal disease (either parietal or occipital). Four (15%) were in mainstream schools but in a class with lower age groups than their own, and 11 children (41%) were in special institutions. Complications and Death Worsening motor deficits developed in 10 patients im- J. Neurosurg: Pediatrics / Volume 106 / January,

5 M. Bourgeois et al. FIG. 1. Preoperative and postoperative neurological studies. A: Typical preoperative MR images showing the cortical angiomatosis. B: A preoperative CT scan revealing calcification in the right occipital region. C: Postoperative MR images confirming complete resection. mediately following surgery, eight of whom had undergone hemispherectomy and two excision of frontoparietal lesions. Three of the five patients who underwent an anatomical hemispherectomy subsequently required cerebrospinal fluid shunt placement. Six patients underwent more than one operation: four because of residual lesion and two because a large angioma in the scalp and the skull necessitated a two-step procedure to reduce the risk of massive hemorrhage. There were no deaths in this series. Treatment Failures In terms of epilepsy control, there were seven treatment failures. There were no treatment failures in the hemispherectomy group. Six of the failures occurred in children who underwent a partial excision. In these six patients, five underwent incomplete resection because of the lesion s proximity to eloquent brain (motor cortex in three, language cortex in one, and visual cortex in one), and one patient (Case 1) with an occipital lesion was treated with partial resection and has since entered the adult population with very poorly controlled seizures (Engel Class IVb). Discussion This retrospective analysis represents the largest review to date of surgery performed at a single institution to treat epilepsy in children with SWS. The study comprises only those patients with intractable epilepsy in whom medical therapy was deemed to have failed. As such, the initial patient characteristics of this group do not represent the SWS population as a whole. This group nevertheless is heterogeneous. Some children underwent surgery early in life, and others underwent surgery in their teenage years after experiencing a long history of seizures. Barely more than half of the children had cutaneous manifestations of SWS. Before the widespread availability of CT scanning and MR imaging for the investigation of epilepsy, facial angiomas occurred in 96 to 100% of patients. 18,23,26,29,35 With the advent of these imaging techniques, it is now known that some patients can have leptomeningeal angiomas without cutaneous manifestations. 2,10,32 In the present study, the presence of a facial nevus was associated with an earlier onset of seizures. This association has not previously been demonstrated. We did not find any correlation between the extent of facial nevi and the extent 24 J. Neurosurg: Pediatrics / Volume 106 / January, 2007

6 Epilepsy surgery in Sturge Weber syndrome FIG. 2. Magnetic resonance images. The functional hemispherectomy (disconnection of one cerebral hemisphere) shown here is the procedure of choice in treating hemispheric SWS as it seems to lower the risk of subsequent hydrocephalus and hemosiderosis. It is usually facilitated by the atrophy of the involved hemisphere. of intracranial disease on imaging. The leptomeningeal angioma, however, was ipsilateral to the facial nevus in all cases. Glaucoma was present in only 22% of the children in this series, which is considerably less than that (48%) found by Sujansky and Conradi 35 in a questionnaire-based study of adults and children. There was a high prevalence of visual field defects (67%) in our study. Given that at the time of surgery nearly half of the children were younger than 5 years of age and it was difficult to examine them for visual field deficits, this value is probably an underestimation. Seizures are also a common feature of SWS and occur in TABLE 3 Postoperative characteristics in 27 children with SWS who underwent surgery for intractable epilepsy Case Location of Resection Degree of Age at Follow-Up Modified Postop Change in No. or Method Resection Side Op (mos) Duration (mos) Engel Class Developmental Status Status 1 occipital partial lt IVb severe none 2 parietooccipital complete rt IIa mild improved 3 parietal complete lt Ia normal improved 4 hemispherectomy complete lt Ia moderate improved 5 hemispherectomy complete lt Ia mild improved 6 hemispherectomy complete lt Ia normal improved 7 temporooccipital complete lt Ia normal improved 8 temporooccipital partial lt Ic mild none 9 parietal partial lt Ib normal none 10 temporooccipital complete rt Ia mild worsened 11 occipital partial rt Ia moderate improved 12 temporal complete rt Ia moderate none 13 temporal partial lt Ib moderate none 14 hemispherectomy complete lt Ia mild improved 15 hemispherotomy complete rt Ia mild improved 16 parietooccipital partial lt IIa normal improved 17 parietooccipital partial rt IIa normal none 18 occipital partial lt IIb normal none 19 frontoparietal partial lt Ia mild improved 20 occipital complete rt Ia normal improved 21 parietal complete rt Ia normal none 22 hemispherotomy complete rt Ia moderate improved 23 frontotemporoparietal complete lt Ia mild improved 24 temporoparietooccipital partial lt Ia mild improved 25 parietooccipital complete lt Ia moderate improved 26 hemispherotomy complete lt Ia severe none 27 hemispherotomy complete rt Ia severe none J. Neurosurg: Pediatrics / Volume 106 / January,

7 M. Bourgeois et al. TABLE 4 Developmental and seizure-related outcome depending on type of epilepsy surgery in 27 children with SWS Epilepsy (%) Developmental Status (%) No No Type of Op Seizures Seizures Improvement Improvement Total hemispherectomy 8 (100) 0 (0) 6 (75) 2 (25) 8 complete resection 8 (89) 1 (11) 6 (67) 3 (33) 9 incomplete resection 3 (30) 7 (70) 4 (40) 6 (60) 10 total 19 (70) 8 (30) 16 (59) 11 (41) to 93% of cases. 3,28,29,35 It was noted that seizures are more prevalent, begin earlier in life, and are associated with more severe developmental delay in the 14% of children who have bilateral leptomeningeal disease. 3 All our patients were unilaterally affected. It is well established that early-onset seizures are more difficult to control and are associated with a worse neurological outcome. 4,35 Eighty-one percent of patients in the present study were developmentally delayed preoperatively. In a questionnairebased study in which 171 patients with SWS were examined, Sujansky and Conradi 35 reported that 58% had developmental delay. This differed between those who had seizures (71%) and those who did not (6%). In other surgical studies of SWS in which patients with seizures are universally represented, the rate of developmental delay ranges from 60 to 100%. 2,6,21,34,36 It is well established that early-onset seizures are more difficult to control and are associated with a worse neurological outcome than those that begin later in life. 4,35 Hoffman and colleagues 18 reported that children whose seizures began in the 1st year of life were more likely to suffer motor deficits and developmental delay. Oakes 26 examined 30 patients who had SWS and reached the same conclusions. Sujansky and Conradi 35 also noted less developmental delay in those whose seizures began later. Kramer and colleagues 22 reviewed 15 patients with SWS and noted that intellectual outcome was correlated with the severity of seizures between the ages of 6 and 18 months of age, but not with the age of onset. In their series, however, all patients had seizure onset when they were younger than 1 year of age. Our findings concur with those of Hoffman, Sujansky, Oakes, and their colleagues and confirm that in children whose seizures started when they were younger than 1 year of age, hemiparesis, intellectual delay, and status epilepticus are significantly more likely to develop. The mechanism as to how neurological impairment occurs in patients with SWS is unclear. Using xenon-enhanced CT scanning, Okudaira et al. 28 succeeded in measuring regional blood flow before and after acetazolamide administration in patients with SWS. The changes in cerebral blood flow (acetazolamide vasoreactivity) were less in those areas remote from the lesion in patients who exhibited clinical progression of their disease. This finding suggests that the hemodynamic compromise (such as that which occurs during the increased metabolic demands of a seizure) contributes to the clinical deterioration. Garcia et al. 16 reported on two patients whose neurological conditions deteriorated as a result of recurrent thrombotic episodes rather than seizures. Jansen et al. 20 also reported strokelike episodes in patients with SWS and suggested that in some cases clinical deterioration could be related to ischemia and discussed the prophylactic use of aspirin in these patients. Others have suggested that the calcifications and atrophy seen in patients with SWS are caused by a vascular steal by the overlying angioma and venous congestion due to a lack of normal cortical venous drainage. 13,25,31 This would be exacerbated by an additional oxygen debt from repeated seizures. It is generally accepted that early-onset seizures are associated with worse neurological and developmental outcomes (a reflection of the extent of the disease and its associated vascular anomalies or the severity of the seizures themselves). The controversy, however, really begins with why and when surgical treatment should be considered and how it should be performed. How long should seizures remain uncontrolled medically before their intractability requires surgery? Should surgery only be considered if there is progressive deterioration in neurological or psychomotor function? Is hemispherectomy only indicated in those children with hemiparesis? The primary goal of surgery in this series, as in others, was the treatment of the seizures. The secondary objective was to allow for an improvement in any developmental delay. In this series 19 children (70%) with intractable epilepsy became seizure free following surgery. The major determinants of success (Engel Class Ia) were the degree of resection of the angioma and underlying abnormal brain. The success rate was 100% in patients who underwent hemispherectomy. This value is reflected in previous studies in which success rates varied from 44 to 100% (Table 5). We did not find any correlation between preoperative seizure profile, timing of surgery, and success with seizure outcome. Tuxhorn and Pannek 36 found that seizure control was better in those patients who underwent surgery at a later time. It would appear that as long as complete removal or disconnection of the diseased brain is achieved through surgery, delaying the procedure does not compromise eventual epilepsy control. If the timing of surgery does not affect seizure outcome, what then is the role of early surgery? Intuitively, one is reluctant to perform an irreversible procedure that carries with it risks of serious morbidity, particularly in a child with no neurological deficits. There are authors who would, on this basis, advocate a more conservative approach to surgery. 1,21,22 In a group of 52 patients who underwent hemispherectomy for various diseases including SWS, Carson et al. 6 found no improvement in developmental outcome in those children who underwent surgery earlier in life. In our series, developmental status was more likely to improve in children who underwent early surgery. Hoffman and colleagues 18 reported that developmental and motor outcomes improved in children who underwent hemispherectomy when they were younger than 1 year of age because they became seizure free. These authors believed that epilepsy that started in infancy always carried with it a worse prognosis, medical intractability of the seizures, progressive hemiparesis, and mental retardation. They advocated early surgery even before a motor deficit was observed in the hope of preventing further injury to the developing brain. In a later review by the same group, the authors reviewed the cases of 40 patients who underwent epilepsy surgery when they were younger than 3 years of age. 34 The authors maintained that improved development was an important sec- 26 J. Neurosurg: Pediatrics / Volume 106 / January, 2007

8 Epilepsy surgery in Sturge Weber syndrome TABLE 5 Outcomes in previous reported series of patients with SWS who underwent surgery for epilepsy* No. of Seizure Authors & Year Patients Age at Op Op Free (%) Other Outcomes Falconer & Rushworth, yrs hemispherectomy 5 (100) 4 (80%) improved dev Hoffman et al., mo 7 yrs hemispherectomy 5 (71) 5 (71%) normal dev; 6 (86%) im- (6 1 yr) proved MD Di Trapani et al., mos & 3 yrs hemispherectomy 2 (100) 2 improved MD Chevrie et al., , 10, & 16 yrs lobectomy/resection 2 (67) 2 improved dev Ogunmekan et al., mos 9 yrs hemispherectomy 10 (100) 8 (80%) normal dev (early op) Ito et al., mos 4 yrs hemispherectomy 3 (100) 3 (100%) improved dev Sujansky & Conradi, mos 20 yrs hemispherectomy 4 (44) 4 (44%) improved seizures Carson et al., yrs hemispherectomy 1 (33) 1 death Vining et al., yrs hemispherectomy 1 (33) 1 death Sugimoto et al., mos hemispherectomy 4 (80) 2 (40%) improved dev Arzimanoglou et al., mos 34 yrs hemispherectomy; 13 (65) all hemispherectomies seizure free lobectomy/resection; & walking; 60% normal dev callosotomy Kossoff et al., mos 17 yrs hemispherectomy 26 (81) 26 (81%) MD; 20 (63%) moderate to severe delay; 1 aphasia Tuxhorn & Pannek, mos & 1 yr hemispherectomy 2 (100) 2 improved dev * Dev = development; MD = motor deficit. In this study five patients underwent a hemispherectomy, 14 a lobectomy, and one a callostomy. Both children had bilateral disease. ondary goal for these children. Oakes 26 also advocated early surgery in these children, given the bleak natural history associated with medical therapy. In 24 patients with SWS and seizures, 83% had seizures that were uncontrolled or poorly controlled. All patients whose epilepsy began when they were younger than 1 year of age had poorly controlled seizures and were developmentally delayed. Ogunmekan et al. 27 performed surgery in 12 patients with SWS and intractable seizures. Ten underwent surgery when they were younger than 30 months old. These authors reported intellectual impairment only in the two patients who underwent surgery at ages 7 and 9 months. Numerous other authors promote early surgery in children with SWS and early-onset epilepsy. 2,7,11,12,19,30,33,37 In our series, eight children underwent a hemispherectomy (either functional or anatomical). All of these children had a preoperative motor deficit (three had hemiplegia). Six of the children exhibited improvement in their hemiparesis at follow up, and the developmental status improved in all. Authors of many studies have shown that hemispherectomy performed early in life is associated with minimal hemiparesis and optimizes intellectual development. 6,11 13,15,18,21,24, 26,27,30,36,39 Prior to embarking on surgical treatment, it is important to establish the location and extent of the hemangioma. We used CT and/or MR imaging to define the margins of the angiomatosis and calcified regions. Later in the series image guidance techniques were used to enhance surgical accuracy. There are reports that positron emission tomography 9,23 and single-photon emission computed tomography 8,17 studies may further delineate epileptogenic areas of the brain that are not shown on MR images. We have no experience with these modalities, but given the encouraging seizure outcome in those who underwent complete resection it would appear that MR imaging remains a satisfactory planning tool for surgery. It is also essential to acquire electrophysiological data to confirm the laterality and location of the seizure origin when a limited resection or lobectomy is considered. Successful treatment of epilepsy that is unilateral in origin in patients with bilateral disease has been reported. 5,35 We had access to excellent neuropsychological assessment facilities and personnel during the preoperative evaluation and follow-up period. This is an integral component of the initial workup and evaluation of outcome. In younger children undergoing this type of surgery, severe blood loss is not uncommon and it is therefore important that surgery take place in a pediatric institution where age-appropriate anesthesia and postoperative intensive care are available. 33 Conclusions We have found that in children with SWS, the onset of seizures in patients younger than 1 year of age is associated with an increased severity of epilepsy and a higher incidence of developmental delay and motor deficits. We believe, as others, that in these children, early surgery is more likely to lead to improved developmental status. Epilepsy control, however, can be achieved by surgery at any age, as long as there is complete resection or disconnection of the diseased cortex. Children with SWS and early-onset epilepsy should be referred as soon as possible to a specialist in a pediatric epilepsy center for consideration of early surgery. References 1. 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9 M. Bourgeois et al. 4. Bodensteiner JB, Roach ES: Sturge-Weber syndrome. Mt. Freedom, NJ: Sturge-Weber Foundation, Bye AM, Matheson JM, Mackenzie RA: Epilepsy surgery in Sturge-Weber syndrome. Aust Paediatr J 25: , Carson BS, Javedan SP, Freeman JM, Vining EP, Zuckerberg AL, Lauer JA, et al: Hemispherectomy: a hemidecortication approach and review of 52 cases. J Neurosurg 84: , Chevrie JJ, Specola N, Aicardi J: Secondary bilateral synchrony in unilateral pial angiomatosis: successful surgical treatment. J Neurol Neurosurg Psychiatry 51: , Chiron C, Raynaud C, Tzourio N, Diebler C, Dulac O, Zilbovicius M, et al: Regional cerebral blood flow by SPECT imaging in Sturge-Weber disease: an aid for diagnosis. J Neurol Neurosurg Psychiatry 52: , Chugani HT, Mazziotta JC, Phelps ME: Sturge-Weber syndrome: a study of cerebral glucose utilization with positron emission tomography. 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Pediatr Neurol 26: , Verity CM, Strauss EH, Moyes PD, Wada JA, Dunn HG, Lapointe JS: Long-term follow-up after cerebral hemispherectomy: neurophysiologic, radiologic, and psychological findings. Neurology 32: , Villemure JG, Mascott CR: Peri-insular hemispherotomy: surgical principles and anatomy. Neurosurgery 37: , 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 Pediatrics 100: , 1997 Manuscript received July 19, Accepted in final form October 2, Address reprint requests to: Christian Sainte-Rose, M.D., Service de Neurochirurgie Pédiatrique, Hôpital Necker Enfants Malades, 149, rue de Sèvres, Paris Cedex 15, France. christian. sainte-rose@nck.ap-hop-paris.fr. 28 J. Neurosurg: Pediatrics / Volume 106 / January, 2007