Measuring outcome after arterial ischemic stroke in childhood with two different instruments.

BACKGROUND: Assessment of outcome after childhood stroke is important both for clinical practice and for research purposes. The objective of this study was to compare two frequently used outcome measures. METHODS: In 40 children with arterial ischemic stroke (AIS), dichotomized outcome obtained from the Pediatric Stroke Outcome Measure (PSOM) was compared with a dichotomized modified Rankin Scale (mRS) combined with information on type of school attendance. In addition, we compared dichotomized outcome, obtained from the PSOM and the mRS combined with school attendance, with the results of pediatric quality of life (PedsQL) questionnaires and the impressions of the child's general functioning on a visual analogue scale (VAS) that was filled out by parents and investigators. RESULTS: In 35 children (88%), outcome classification was concordant between the two outcome measures. Five children had a poor outcome according to the PSOM and good outcome with the mRS including school performance. In these patients, mRS outcome classification agreed better with the impression of the investigators, as reflected by VAS scores ≥7.5. For both the PSOM and mRS in combination with school performance, patients with a good outcome had significantly higher PedsQL and VAS scores than those with a poor outcome (p values <0.01 for all comparisons). VAS scores of investigators and parents correlated significantly with PedsQL. CONCLUSIONS: In children with AIS, both PSOM and mRS combined with school type correlated significantly with quality of life and VAS scores of general functioning. The mRS combined with school type is easier to obtain than the PSOM, reflects function rather than deficits, includes an important measure of cognitive outcome, and corresponds better with the doctor's impression of outcome.

Contralateral MRI abnormalities affect seizure and cognitive outcome after hemispherectomy.

OBJECTIVE: To explore whether EEG and MRI abnormalities in the "healthy" hemisphere influence seizure and cognitive outcome after functional hemispherectomy. METHODS: This is a retrospective consecutive cohort study of 43 children who underwent functional hemispherectomy between 1994 and 2008. Results of preoperative EEG recordings were reviewed for the existence of (inter)ictal epileptic or background abnormalities in the contralateral hemisphere. Preoperative MRIs were reexamined for the existence of unequivocal contralateral abnormalities. Postoperative seizure status was assessed, and of 34 children, IQ or mental developmental index (MDI) scores were obtained preoperatively and postoperatively. Seizure freedom was defined as Engel 1A. Contralateral EEG and MRI abnormalities were studied in relation to seizure and cognitive outcome. RESULTS: Thirty-three children achieved seizure freedom (77%). Of the 11 patients with contralateral MRI abnormalities, only 45% were seizure free, compared with 88% of the 32 patients without contralateral MRI lesions (p = 0.030). Children with contralateral MRI abnormalities more often were severely retarded after surgery (MDI/IQ <55; 90% vs 42%, p = 0.030). Postoperative MDI/IQ scores improved in none of the children with, but in 38% of those without contralateral MRI abnormalities (p = 0.034). Contralateral epileptic or background EEG abnormalities did not affect seizure outcome or postoperative cognitive performance. Four of 6 children with bilateral epileptic encephalopathy reached seizure freedom. CONCLUSION: Unambiguous contralateral MRI abnormalities are significantly associated with seizure recurrence, severe mental delay, and lack of cognitive improvement and may be considered a relative contraindication for hemispherectomy. Contralateral EEG abnormalities do not negatively influence postsurgical outcome.

Does a preference for fatty foods prior to commencing treatment with the ketogenic diet predict the efficacy of this diet?

The ketogenic diet can be effective in children who suffer from drug-resistant epilepsy. However, it is still hard to predict how large an effect this diet will have for an individual child. Previous data suggests a high-fat food preference is more likely in those with epilepsy, as assessed by in-person forced-choice design. The aim of this study is to examine whether a partiality to fatty foods prior to commencing the ketogenic diet can be used as a predictive factor for the efficacy of this diet in children with drug-resistant epilepsy. Data from 43 children aged between 2 and 19 years was used in this retrospective, non-controlled, non-randomised, open study. All children had followed the ketogenic diet for a period of 3 months or more. Before commencing the diet, a food record was collected for each child to determine the percentage of daily energy-intake accounted for by fats. Parents of the participants completed a questionnaire to measure fat-preference in the pre-diet period and received a score to objectify the efficacy of the treatment. The raw scores on the food record and on the questionnaire were divided into subgroups. Subsequently Kendall's tau-b was calculated for the correlation between each combination of variables. A non-significant correlation was found for the relationship between the food record and the questionnaire (p=.939), the relationship between the food record and the efficacy of the treatment (p=.827) and the relationship between the questionnaire and the efficacy of the treatment (p=.539). This means treatment efficacy cannot be predicted by the child's food preference.

Lateralization of motor innervation in children with intractable focal epilepsy--a TMS and fMRI study.

PURPOSE: To correlate hand function with lateralization of motor innervation, as studied with transcranial magnetic stimulation (TMS) and functional magnetic imaging (fMRI), in children with intractable epilepsy and lesions in the vicinity of the motor cortex. METHODS: In 34 children hand motor function was examined and motor evoked potentials (MEPs) were recorded after TMS of both hemispheres, establishing lateralization of corticospinal innervation. When feasible, patients underwent fMRI using a manual motor task. RESULTS: Good function of the contralesional hand was associated with early lesions (p=0.02). Lateralization of motor innervation to the contralesional hand correlated with quality of motor function (p=0.001); 83% of children with poor hand function had ipsi- or bilateral innervation, whereas all children with good hand function had pure contralateral control. Mirror movements during movement of the unaffected hand predicted ipsilateral contribution to motor innervation (p=0.006). Fourteen children who had no TMS responses were younger than those with elicitable MEPs (p<0.001). TMS led to a temporary increase of seizure frequency in four children. fMRI results were concordant with TMS. CONCLUSIONS: Poor function of the contralesional hand is strongly associated with ipsilateral motor innervation. Reorganization in the lesioned hemisphere mainly occurs in early developmental lesions and seems efficient in maintaining good hand function. Clinical examination of hand function has predictive value for the pattern of motor innervation prior to epilepsy surgery, which in older children can further be established by TMS and fMRI.

Characterization of febrile seizures and febrile seizure susceptibility in mouse inbred strains.

Febrile seizures (FS) are the most prevalent seizures in children. Although FS are largely benign, complex FS increase the risk to develop temporal lobe epilepsy (TLE). Studies in rat models for FS have provided information about functional changes in the hippocampus after complex FS. However, our knowledge about the genes and pathways involved in the causes and consequences of FS is still limited. To enable molecular, genetic and knockout studies, we developed and characterized an FS model in mice and used it as a phenotypic screen to analyze FS susceptibility. Hyperthermia was induced by warm air in 10- to 14-day-old mice and induced FS in all animals. Under the conditions used, seizure-induced behavior in mice and rats was similar. In adulthood, treated mice showed increased hippocampal Ih current and seizure susceptibility, characteristics also seen after FS in rats. Of the seven genetically diverse mouse strains screened for FS susceptibility, C57BL/6J mice were among the most susceptible, whereas A/J mice were among the most resistant. Strains genetically similar to C57BL/6J also showed a susceptible phenotype. Our phenotypic data suggest that complex genetics underlie FS susceptibility and show that the C57BL/6J strain is highly susceptible to FS. As this strain has been described as resistant to convulsants, our data indicate that susceptibility genes for FS and convulsants are distinct. Insight into the mechanisms underlying seizure susceptibility and FS may help to identify markers for the early diagnosis of children at risk for complex FS and TLE and may provide new leads for treatment.

Inflammatory processes in cortical tubers and subependymal giant cell tumors of tuberous sclerosis complex.

Cortical tubers and subependymal giant cell tumors (SGCT) are two major cerebral lesions associated with tuberous sclerosis complex (TSC). In the present study, we investigated immunocytochemically the inflammatory cell components and the induction of two major pro-inflammatory pathways (the interleukin (IL)-1beta and complement pathways) in tubers and SGCT resected from TSC patients. All lesions were characterized by the prominent presence of microglial cells expressing class II-antigens (HLA-DR) and, to a lesser extent, the presence of CD68-positive macrophages. We also observed perivascular and parenchymal T lymphocytes (CD3(+)) with a predominance of CD8(+) T-cytotoxic/suppressor lymphoid cells. Activated microglia and reactive astrocytes expressed IL-1beta and its signaling receptor IL-1RI, as well as components of the complement cascade, such as C1q, C3c and C3d. Albumin extravasation, with uptake in astrocytes, was observed in both tubers and SGCT, suggesting that alterations in blood brain barrier permeability are associated with inflammation in TSC-associated lesions. Our findings demonstrate a persistent and complex activation of inflammatory pathways in cortical tubers and SGCT.

Cognitive impairment in tuberous sclerosis complex is a multifactorial condition.

OBJECTIVE: In patients with tuberous sclerosis complex (TSC), associations between tuber number, infantile spasms, and cognitive impairment have been proposed. We hypothesized that the tuber/brain proportion (TBP), the proportion of the total brain volume occupied by tubers, would be a better determinant of seizures and cognitive function than the number of tubers. We investigated tuber load, seizures, and cognitive function and their relationships. METHODS: Tuber number and TBP were characterized on three-dimensional fluid-attenuated inversion recovery MRI with an automated tuber segmentation program. Seizure histories and EEG recordings were obtained. Intelligence equivalents were determined and an individual cognition index (a marker of cognition that incorporated multiple cognitive domains) was calculated. RESULTS: In our sample of 61 patients with TSC, TBP was inversely related to the age at seizure onset and to the intelligence equivalent and tended to be inversely related to the cognition index. Further, a younger age at seizure onset or a history of infantile spasms was related to lower intelligence and lower cognition index. In a multivariable analysis, only age at seizure onset and cognition index were related. CONCLUSIONS: Our systematic analysis confirms proposed relationships between tuber load, epilepsy and cognitive function in tuberous sclerosis complex (TSC), but also indicates that tuber/brain proportion is a better predictor of cognitive function than tuber number and that age at seizure onset is the only independent determinant of cognitive function. Seizure control should be the principal neurointervention in patients with TSC.

Overlapping neurologic and cognitive phenotypes in patients with TSC1 or TSC2 mutations.

OBJECTIVE: The purpose of this study was to systematically analyze the associations between different TSC1 and TSC2 mutations and the neurologic and cognitive phenotype in patients with tuberous sclerosis complex (TSC). METHODS: Mutation analysis was performed in 58 patients with TSC. Epilepsy variables, including EEG, were classified. A cognition index was determined based on a comprehensive neuropsychological assessment. On three-dimensional fluid-attenuated inversion recovery MR images, an automated tuber segmentation program detected and calculated the number of tubers and the proportion of total brain volume occupied by tubers (tuber/brain proportion [TBP]). RESULTS: As a group, patients with a TSC2 mutation had earlier age at seizure onset, lower cognition index, more tubers, and a greater TBP than those with a TSC1 mutation, but the ranges overlapped considerably. Familial cases were older at seizure onset and had a higher cognition index than nonfamilial cases. Patients with a mutation deleting or directly inactivating the tuberin GTPase activating protein (GAP) domain had more tubers and a greater TBP than those with an intact GAP domain. Patients with a truncating TSC1 or TSC2 mutation differed from those with nontruncating mutations in seizure types only. CONCLUSIONS: Although patients with a TSC1 mutation are more likely to have a less severe neurologic and cognitive phenotype than those with a TSC2 mutation, the considerable overlap between both aspects of the phenotype implies that prediction of the neurologic and cognitive phenotypes in individuals with tuberous sclerosis complex should not be based on their particular TSC1 or TSC2 mutation.

Epilepsy surgery in tuberous sclerosis: the Dutch experience.

INTRODUCTION: Epilepsy associated with tuberous sclerosis complex (TSC) is drug resistant in more than half of the patients. Epilepsy surgery may be an alternative treatment option, if the epileptogenic tuber can be identified reliably and if seizure reduction is not at the expense of cognitive or other functions. We report the pre-surgical identification of the epileptogenic tuber and post-surgical outcome of patients with TSC in The Netherlands. METHODS: Twenty-five patients underwent the pre-surgical evaluation of the Dutch Comprehensive Epilepsy Surgery Programme, including a detailed seizure history, interictal and ictal video EEG registrations, 3D FLAIR MRI scans and neuropsychological testing. Suitability of the candidates was decided in consensus. Seizure outcome, scored with the Engel classification, and cognition were reassessed at fixed post-surgery intervals. RESULTS: Epilepsy surgery was performed in six patients. At follow-up, four patients had Engel classification 1, two had classification 4. Improved development and behaviour was perceived by the parents of two patients. Epilepsy surgery was not performed in 19 patients because seizures were not captured, ictal onset zones could not be localised or were multiple, interictal EEG, video EEG and MEG results were not concordant, or seizure burden had diminished during decision making. A higher cognition index was found in the surgical patients compared to the non-surgical candidates. CONCLUSIONS: Epilepsy surgery can be performed safely and successfully in patients in whom semiology, interictal EEG, ictal EEG, MEG and the location of tubers are concordant. In other cases the risk of surgery should be weighed against the chance of seizure relief and in case of children subsequent impact on neurodevelopment.

Familial occurrence of brain arteriovenous malformations: a systematic review.

BACKGROUND: Brain arteriovenous malformations (BAVMs) are thought to be sporadic developmental vascular lesions, but familial occurrence has been described. We compared the characteristics of patients with familial BAVMs with those of patients with sporadic BAVMs. METHODS: We systematically reviewed the literature on patients with familial BAVMs. Three families that were found in our centre were added. Age, sex distribution and clinical presentation of the identified patients were compared with those in population based series of patients with sporadic BAVMs. Furthermore, we calculated the difference in mean age at diagnosis of parents and children to study possible anticipation. RESULTS: We identified 53 patients in 25 families with BAVMs. Mean age at diagnosis of patients with familial BAVMs was 27 years (range 9 months to 58 years), which was younger than in the reference population (difference between means 8 years, 95% CI 3 to 13 years). Patients with familial BAVMs did not differ from the reference populations with respect to sex or mode of presentation. In families with BAVMs in successive generations, the age of the child at diagnosis was younger than the age of the parent (difference between means 22 years, 95% CI 13 to 30 years), which suggests clinical anticipation. CONCLUSIONS: Few patients with familial BAVMs have been described. These patients were diagnosed at a younger age than sporadic BAVMs whereas their mode of presentation was similar. Although there are indications of anticipation, it remains as yet unclear whether the described families represent accidental aggregation or indicate true familial occurrence of BAVMs.

[Intracranial EEG monitoring for epilepsy surgery using electrode grids--results in the first 22 Dutch patients]. / Intracranieel eeg-onderzoek met elektrodematjes ten behoeve van epilepsiechirurgie; resultaten bij de eerste 22 patiënten.

OBJECTIVE: Description of initial experiences with subdural electrode grids in patients with refractory focal epilepsy as additional diagnostic tool for epilepsy surgery. Using these electrodes, the attacks were recorded during a number of days and the cerebral cortex was electrically stimulated in order to map the functional areas. DESIGN: Retrospective. METHOD: Data were collected from patients in whom subdural electrode grids had been placed between 1 September 1999 and 31 August 2004. All patients underwent a neurological examination and a neuropsychological test before the implantation. At the follow-up examination, the results with regard to function and the frequency of attacks were noted, as well as the complications. RESULTS: Electrodes were placed in 22 patients: 9 women and 13 men with an average age of 27 years (range: 5-42). The implantation lasted for an average of 7 days (range: 3-10). In 4 patients, increased seizures during implantation required intravenous anticonvulsant treatment. Severe but transitory complications were seen in 4 patients (meningitis, subdural haematoma and ischaemia). 19 patients underwent a therapeutic resection. A postoperative decline in language skills was noted in 1 patient, while another 2 scored poorer in verbal tests. A permanent decline in sensorimotor function was seen in 1 patient, but this had been foreseen. Of the 16 operated patients with a duration of follow-up of at least 1 year, so were (practically) free of attacks, and another 3 patients had significantly fewer attacks. CONCLUSION: Registration with intracranial electrodes makes it possible to treat epileptic patients surgically by excision of brain tissue near critical areas. Such intensive monitoring is, however, not without risk and this must be weighed against the potential benefits.

Thrombin-stimulated glutamate uptake in human platelets is predominantly mediated by the glial glutamate transporter EAAT2.

Glutamate toxicity has been implicated in the pathogenesis of various neurological diseases. Glial glutamate transporters play a key role in the regulation of extracellular glutamate levels in the brain by removing glutamate from the extracellular fluid. Since human blood platelets possess an active glutamate uptake system, they have been used as a peripheral model of glutamate transport in the central nervous system (CNS). The present study is aimed at identifying the glutamate transporter on blood platelets, and to asses the influence of platelet activation on glutamate uptake. Platelets from healthy donors showed Na+-dependent glutamate uptake (Km, 3.5+/-0.9 microM; Vmax, 2.8+/-0.2 pmol glutamate/75 x 10(6)platelets/30 min), which could be blocked dose-dependently by the EAAT specific inhibitors DL-threo-E-benzyloxyaspartate (TBOA), L-trans-pyrrolidine-2,4-dicarboxylic acid (tPDC) and high concentrations of the EAAT2 inhibitor dihydrokainate (DHK). Analysis of platelet homogenates on Western blots showed EAAT2 as the predominant glutamate transporter. Platelet activation by thrombin caused an increase in glutamate uptake, which could be inhibited by TBOA and the EAAT2 inhibitor DHK. Kinetic analysis showed recruitment of new transporters to the membrane. Indeed, Western blot analysis of subcellular fractions revealed that alpha-granules, which fuse with the membrane upon thrombin stimulation, contained significant EAAT2 immunoreactivity. Inhibition of the second messengers involved in alpha-granule secretion (protein kinase C, phosphatidylinositol-3-kinase) inhibited thrombin-stimulated uptake, but not basal uptake. These data show that the glial EAAT2 is the predominant glutamate transporter on blood platelets and suggest, that thrombin increases glutamate uptake capacity by recruiting new transporters (EAAT2) from alpha-granules.

Propofol and thiopental for refractory status epilepticus in children.

To assess safety and efficacy of propofol and thiopental for refractory status epilepticus (RSE) in children, the authors reviewed 34 episodes of RSE. Thiopental was effective in most patients, but there were serious side effects. Propofol was used according to a strict protocol. It was effective in most patients, so that thiopental was not needed. Side effects were infrequent, of minor severity, and fully reversible. The authors suggest the use of propofol before thiopental.

Role of visual dysfunction in postural control in children with cerebral palsy.

INTRODUCTION: Deficient postural control is one of the key problems in cerebral palsy (CP). Little, however, is known about the specific nature of postural problems of children with CP, nor of the relation between abnormal posture and dysfunction of the visual system. AIM OF THE STUDY: To provide additional information on the association of abnormalities in postural control and visual dysfunction of the anterior or posterior part of the visual system. METHODS: Data resulting from ophthalmologic, orthoptic, neurological, neuro-radiological, and ethological investigations of more than 313 neurologically impaired children were retrospectively analyzed. RESULTS: Abnormal postural control related to ocular and ocular motor disorders consisted of anomalous head control and subsequent abnormal head posture and torticollis. The abnormal postural control related to retrochiasmatical damage of the visual system consisted of a torticollis combined with adjustment of the upper part of the body, as if at the same time adapting to a combination of defects and optimizing residual visual functions. CONCLUSION: Visual dysfunctions play a distinct role in the postural control of children with CP.

Clinical presentation, associated disorders and aetiological moments in Cerebral Palsy: a Dutch population-based study.

PURPOSE: Cerebral Palsy (CP) contains varying clinical presentations, associated disorders and aetiological moments. Quantitative data and trends on these aspects were lacking in The Netherlands. METHOD: Within a population-based study on prevalence, presentation and functioning of Dutch children with CP born in the years 1977-1988, individual history taking, examination and medical file checking was done by experienced clinicians. Clinical subtypes, motor disability, important co-morbidity (mental retardation, visual disability and epilepsy) were recorded, aetiological moments identified if possible. By comparing the four most recent years with the earlier years possible trends were studied. RESULTS: A quarter of children beforehand recorded as CP did not meet inclusion criteria after individual examination. Spastic subtypes accounted for over 90% of all CP cases: bilateral spastic cerebral palsy as a group are the majority although spastic hemiplegia is percentage-wise the largest individual clinical subtype. Epilepsy and mental retardation are common. Clinical patterns and associated disorders remained rather constant comparing earlier to more recent birth years. CONCLUSIONS: An early diagnosis of CP may be challenged. General clinical patterns remained rather constant in following years, as did most studied items. Even if this study revealed a prevalence rise, no aspect stood out as a possible explanation for this prevalence rise. Comparable studies performed elsewhere showed similar findings.

Epilepsy surgery does not harm motor performance of children and adolescents.

The impact of epilepsy surgery on motor performance, activities of daily life (ADL) and caregiver assistance was assessed in 37 children (age range 0.1-15.4 years) with pharmacologically untreatable epilepsy, 17 of whom were also diagnosed as having spasticity of cerebral origin. All patients underwent epilepsy surgery between 1996 and 2001 at the Wilhelmina University Children's Hospital and were assessed using a standard protocol at fixed intervals: before surgery and 6 months, 1 year and 2 years after surgery. The type of surgery was hemispherectomy (n = 14) and temporal (n = 14), frontal (n = 4), parietal (n = 2) and central (n = 2) resection. One child underwent callosotomy. Engel's classification was used to determine seizure outcome. Impairments were measured in terms of muscle strength, range of motion and muscle tone. Motor performance of infants and children without spasticity was measured using the Movement Assessment Battery for Children (M-ABC). The Gross Motor Function Measure (GMFM-88) was used in children with spasticity, the severity of motor disability in this group being determined by means of the Gross Motor Function Classification System (GMFCS). Daily activities and caregiver's assistance were measured in all children using the Pediatric Evaluation of Disability Inventory (PEDI). Twenty-four months after surgery 74% of the children could be classified as Engel class 1, indicating a significant seizure reduction. Impairments revealed some decrease in muscle strength and range of motion in the group with spasticity. Scores improved statistically significantly at group level on M-ABC and GMFM (P < 0.05). Improvement in activities of daily life and caregiver's assistance could not be measured in children without spasticity because of the ceiling effect of the PEDI, but children with spasticity improved significantly with respect to these parameters (PEDI) (P < 0.05). Hence, epilepsy surgery does not harm motor performance in children with or without spasticity.

Differential localization of hamartin and tuberin and increased S6 phosphorylation in a tuber.

In a tuberous sclerosis patient with a mutation in the TSC1 tumor suppressor gene, no second-hit mutation was found in a resected cortical tuber. Tuber giant cells showed predominantly nuclear hamartin, cytosolic tuberin, and hyperphosphorylation of S6. Differential accumulation of hamartin and tuberin in separate cellular compartments of giant cells may prevent formation of the hamartin-tuberin complex, resulting in increased S6 phosphorylation. These data provide an alternative mechanism for tuberogenesis.

Alternative splicing of glutamate transporter EAAT2 RNA in neocortex and hippocampus of temporal lobe epilepsy patients.

RATIONALE: Altered expression of glutamate transporter EAAT2 protein has been reported in the hippocampus of patients with temporal lobe epilepsy (TLE). Two alternative EAAT2 mRNA splice forms, one resulting from a partial retention of intron 7 (I7R), the other from a deletion of exon 9 (E9S), were previously implicated in the loss of EAAT2 protein in patients with amyotrophic lateral sclerosis. METHODS: By RT-PCR we studied the occurrence of I7R and E9S in neocortical and hippocampal specimens from TLE patients and non-neurological controls. RESULTS: Both splice forms were found in all neocortical specimens from TLE patients (100% I7R, 100% E9S). This was significantly more than in controls (67% I7R, 60% E9S; P < 0.05). We also detected I7R and E9S in all seven motor cortex post-mortem samples from patients with amyotrophic lateral sclerosis. Within the TLE patient group, both splice variants appeared significantly more in non-sclerotic (100%), than in sclerotic hippocampi (69%, P < 0.05). CONCLUSION: These data indicate that the epileptic brain, especially that of TLE patients without hippocampal sclerosis, is highly prone to alternative EAAT2 mRNA splicing. Our data confirm that the presence of alternative EAAT2 splice forms is not disease specific.

Functional consequences of hemispherectomy.

Using the International Classification of Functioning Disability and Health (ICF) (WHO, 2001), impairments, activities and social participation are reported in 12 children (mean age at surgery 5.9 years) who were investigated before and three times over a 2-year period after hemispherectomy. Impairments were assessed (i) in terms of seizure frequency (Engel classification) and seizure severity (HASS) and (ii) with respect to muscle strength (MRC), range of motion (JAM score) and muscle tone (modified Ashworth scale). Activities were assessed in terms of gross motor functioning (GMFM) and self-care, mobility and social function (PEDI). Participation was assessed in terms of epilepsy-related restrictions and quantified by means of the Hague Restrictions in Childhood Epilepsy Scale (HARCES). Nine out of 12 children could be classified as free of seizures (Engel class I), and in the remaining three seizure frequency was Engel class III. HASS scores showed maximum improvement in 10 out of 12 children and near-maximum improvement in the two remaining children. Muscle strength and muscle tone on the side of the body contralateral to the hemispherectomy, which were already decreased preoperatively, decreased even further in the first 6 months after surgery, but returned to the presurgical baseline thereafter, except for the distal part of the arm. Range of motion was abnormal prior to operation and remained so after operation. Mean GMFM increase was 20% after 2 years (95% confidence interval 10-33); all five dimensions improved statistically significantly (P < 0.05). Mean PEDI increase was more than 20 scale points (95% confidence interval 10-35); again, all domains improved significantly (P < 0.05). In nearly all children, HARCES scores had normalized 2 years after surgery. In conclusion, decrease of seizure frequency and severity widens the scope of motor and social functioning, which overrides the effects of remaining motor impairments.