Could prevention of infantile spasms have been possible in a historical cohort of 31 tuberous sclerosis patients?

Efforts to prevent epilepsy in infants with tuberous sclerosis complex (TSC) has been the focus of EPISTOP. PURPOSE: The present study was carried out to evaluate whether prevention could have been realistic. METHODS: A retrospective analysis by hospital chart review of 31 patients with TSC and infantile spasms (practically all patients) admitted to two tertiary hospitals, Children's Hospital, University of Helsinki and Kuopio in 1980-2000. Clinical history, early cognitive development, early clinical signs of TSC, clinical signs of suspicious seizures, first seizures and EEG, response to adrenocorticotropic hormone (ACTH) therapy, EEG and brain imaging were evaluated. RESULTS: Early development prior the spasms was apparently normal in 25 (80%). The first EEG ever performed for a child showed hypsarrhythmia in 16 (51%) or modified hypsarrhythmia in 10 (32%). Treatment lag was short (0-4, mean 2 weeks) and the primary response to ACTH favorable in 19 (64%). Etiological diagnostic workup of IS revealed TSC. In one single case (3%) the diagnosis of TSC could be made at birth due to a congenital cardiac rhabdomyoma. Three other rhabomyomas were diagnosed later. In brain imaging, subependymal periventricular calcifications or hypodense areas were seen in every patient at onset of IS. Other organ manifestations of TSC were retinal phakomas (6), polycystic kidneys (2), and renal angiolipomatosis (1). CONCLUSIONS: Preventive treatment of epileptic discharges could have been possible in a single case of neonatal rhabdomyoma suggesting that preventive treatment is challenging in everyday practice. The main obstacle is the delay of TSC diagnosis.

Prevention of infantile spasms in tuberous sclerosis complex.

Since the ground-breaking work of Gomez in the 1970s and the later epidemiological studies of Webb and Osborne [1], the link between early onset epilepsy, especially infantile spasms (IS), and intellectual disability in tuberous sclerosis complex (TSC) has been accepted. This association raises the question of whether prevention of epilepsy in early life in TSC patients may improve the longer-term cognitive outcome.

Prevention of Epilepsy in Infants with Tuberous Sclerosis Complex in the EPISTOP Trial.

OBJECTIVE: Epilepsy develops in 70 to 90% of children with tuberous sclerosis complex (TSC) and is often resistant to medication. Recently, the concept of preventive antiepileptic treatment to modify the natural history of epilepsy has been proposed. EPISTOP was a clinical trial designed to compare preventive versus conventional antiepileptic treatment in TSC infants. METHODS: In this multicenter study, 94 infants with TSC without seizure history were followed with monthly video electroencephalography (EEG), and received vigabatrin either as conventional antiepileptic treatment, started after the first electrographic or clinical seizure, or preventively when epileptiform EEG activity before seizures was detected. At 6 sites, subjects were randomly allocated to treatment in a 1:1 ratio in a randomized controlled trial (RCT). At 4 sites, treatment allocation was fixed; this was denoted an open-label trial (OLT). Subjects were followed until 2 years of age. The primary endpoint was the time to first clinical seizure. RESULTS: In 54 subjects, epileptiform EEG abnormalities were identified before seizures. Twenty-seven were included in the RCT and 27 in the OLT. The time to the first clinical seizure was significantly longer with preventive than conventional treatment [RCT: 364 days (95% confidence interval [CI] = 223-535) vs 124 days (95% CI = 33-149); OLT: 426 days (95% CI = 258-628) vs 106 days (95% CI = 11-149)]. At 24 months, our pooled analysis showed preventive treatment reduced the risk of clinical seizures (odds ratio [OR] = 0.21, p = 0.032), drug-resistant epilepsy (OR = 0.23, p = 0.022), and infantile spasms (OR = 0, p < 0.001). No adverse events related to preventive treatment were noted. INTERPRETATION: Preventive treatment with vigabatrin was safe and modified the natural history of seizures in TSC, reducing the risk and severity of epilepsy. ANN NEUROL 2021;89:304-314.

Vigabatrin with hormonal treatment versus hormonal treatment alone (ICISS) for infantile spasms: 18-month outcomes of an open-label, randomised controlled trial.

BACKGROUND: Infantile spasms constitute a severe form of epileptic encephalopathy. In the International Collaborative Infantile Spasms Study (ICISS), we showed that combining vigabatrin with hormonal therapy was more effective than hormonal therapy alone at stopping spasms between days 14 and 42 of treatment. In this planned follow-up, we aimed to assess whether combination therapy was associated with improved developmental and epilepsy outcomes at 18 months of age. METHODS: In ICISS, a multicentre, open-label, randomised controlled trial, infants were enrolled from 102 hospitals (three in Australia, 11 in Germany, two in New Zealand, three in Switzerland, and 83 in the UK). Eligible infants had a clinical diagnosis of infantile spasms and a hypsarrhythmic (or similar) electroencephalogram (EEG) no more than 7 days before enrolment. Participants were randomly assigned (1:1) by a secure website to receive hormonal therapy with vigabatrin or hormonal therapy alone. If parents consented, there was an additional randomisation (1:1) of type of hormonal therapy used (prednisolone or tetracosactide depot). Block randomisation was stratified for hormonal treatment and risk of developmental impairment. Parents and clinicians were not masked to therapy, but investigators assessing epilepsy and developmental outcomes at 18 months were masked to treatment allocation. Minimum doses were oral prednisolone 10 mg four times a day or intramuscular tetracosactide depot 0·5 mg (40 IU) on alternate days with or without oral vigabatrin 100 mg/kg per day. The primary outcome at 18 months was development as assessed by the Vineland Adaptive Behaviour Scales (VABS) composite score. Secondary outcomes were the presence or absence of epileptic seizures or infantile spasms in the previous 28 days, as recorded by parents and carers, and the use of any anti-epileptic treatment (including ketogenic diet) in the previous 28 days. Analysis was by intention to treat. The trial is registered with the ISRCTN registry, number 54363174, and EudraCT, number 2006-000788-27. FINDINGS: Between March 7, 2007, and May 22, 2014, 766 infants were screened and, of those, 377 were randomly assigned to hormonal therapy with vigabatrin (n=186) or hormonal therapy alone (n=191). 362 infants were assessed for developmental and epilepsy outcomes at 18 months, 181 in each treatment group. Mean VABS scores did not differ significantly between the combination therapy group and the hormonal therapy alone group (73·9 [SE 1·3] vs 72·7 [1·4], difference -1·2 [95% CI -4·9 to 2·6], p=0·55). Presence of epilepsy at the assessment at age 18 months was similar in both treatment groups (54 [30·0%] of 180 infants who received combination therapy vs 52 [29·2%] of 178 who received hormonal therapy alone; difference 0·8% [95% CI -8·8 to 10·4], p=0·90). Presence of spasms was also similar in both treatment groups (27 [15·0%] of 180 infants on combination therapy vs 28 [15·7%] of 178 on hormonal therapy alone; difference 0·7% [95% CI -6·9 to 8·3], p=0·85). At the 18-month assessment, 158 (44·1%) of 358 infants were on some form of anti-epileptic treatment. Initial control of spasms between days 14 and 42 of treatment was associated with higher mean VABS scores at 18 months (79·1 [SE 1·2] vs 63·2 [1·1], difference 15·9 [95% CI 12·4 to 19·5], p<0·001) and with higher likelihood of absence of seizures at 18 months (in 39 [17·0%] of 229 infants who achieved spasm cessation vs 67 [51·9%] of 129 who did not; difference 34·9% [24·8 to 45·0], p<0·001). Increasing lead-time to treatment was associated with lower VABS scores (analysis of variance: F[4,354]=6·38, p<0·001) and worse epilepsy outcomes (p=0·023). INTERPRETATION: Combination therapy did not result in improved developmental or epilepsy outcomes at 18 months. However, early clinical response to treatment was associated with improved developmental and epilepsy outcomes at 18 months. Longer lead-time to treatment was associated with poorer outcomes. Rapid diagnosis and effective treatment of infantile spasms could therefore improve outcomes. FUNDING: The Castang Foundation, Bath Unit for Research in Paediatrics, National Institute of Health Research, the Royal United Hospitals Bath NHS Foundation Trust, BRONNER-BENDER Stiftung/Gernsbach, University Children's Hospital Zurich.

Alteraciones reversibles en la neuroimagen asociadas al tratamiento con vigabatrina en lactantes con espasmos epilépticos / Reversible alterations in the neuroimages associated with vigabatrine treatment in infants with epileptic spasms

Introducción. La vigabatrina (VGB) es un fármaco de primera línea para el tratamiento de espasmos infantiles. Diversos estudios han hallado anomalías en la resonancia magnética (RM) cerebral, que afectaban particularmente a los ganglios de la base, y especialmente en secuencias de difusión, en lactantes con espasmos que recibían VGB en altas dosis (> 100 mg/kg/día), y se ha observado la desaparición de las lesiones tras la retirada de dicho tratamiento. Casos clínicos. Se presentan dos casos clínicos con inicio de una encefalopatía epiléptica en el primer año de vida y crisis en forma de espasmos infantiles. Ambos recibieron tratamiento con distintos fármacos, entre ellos VGB hasta dosis de 200 mg/kg/día. Con 11 y 28 meses de vida, respectivamente, aparecían imágenes en la RM cerebral con una marcada hiperintensidad de señal en secuencias ponderadas en T2 en ambos pálidos, tálamos, porción posterior del tronco encefálico y núcleos dentados, que asociaban restricción en secuencias de difusión. Ambos disponían de estudios previos de RM, sin alteraciones. Tras excluir una metabolopatía subyacente, se decidió la retirada de la VGB y tres meses después, en una RM de control, se apreció la total reversibilidad de dichas lesiones. Conclusiones. Deben evaluarse con cautela los hallazgos de la RM cerebral en lactantes que reciban VGB en altas dosis para el tratamiento de espasmos. Su aparente efecto citotóxico sobre los ganglios de la base podría simular metabolopatías/ enfermedades mitocondriales. Conocer este efecto de la VGB y sus características típicas en la RM puede evitar pruebas innecesarias, como una biopsia muscular o un nuevo cribado metabólico (AU)

Introduction. Vigabatrin (VGB) is a first-line drug for the treatment of infantile spasms. Recently, several reports claim the existence of abnormalities in magnetic resonance imaging (MRI) (particularly affecting basal ganglia, and visible in T2 and diffusion sequences) in infants with spasms that were receiving high doses of VGB (> 100 mg/kg/day), which appear to be reversible after withdrawal of treatment. Case reports. We present two cases with an epileptic encephalopathy in the first year of life and seizures consisting of infantile spasms. Both were treated with several antiepileptic drugs, including VGB up to a maximum dosage of 200 mg/ kg/day. At the age of 11 and 28 months, respectively, MRI images showed marked signal hyperintensities on T2-sequences on bilateral globus pallidus, thalamus, posterior portion of the brainstem and dentate nuclei, also visible on diffusion sequences. Both had previous unaltered MRI studies. After excluding an underlying metabolic disease, VGB withdrawal is decided, appreciating the reversibility of those lesions in a prospective MRI study, three months later. Conclusions. We must consider and carefully evaluate findings on brain MRI in infants receiving VGB at high doses for treatment of spasms. The apparent cytotoxic effect on basal ganglia could simulate metabolic/mitochondrial diseases. By knowing this effect of VGB and its typical MRI features, unnecessary testing can be avoided in young infants with epileptic encephalopathies, including complex procedures like muscle biopsy or a new metabolic screening (AU)

Prevention of infantile spasms relapse: Zonisamide and topiramate provide no benefit.

OBJECTIVE: There is scant evidence to guide the management of infantile spasms after successful response to initial therapies. There is significant risk of relapse, largely because effective pharmacologic treatments cannot be continued long term because of concern for significant adverse events. Zonisamide (ZNS) and topiramate (TPM) are commonly used to prevent relapse, and the purpose of this study was to specifically evaluate the efficacy of ZNS and TPM as agents for secondary prevention of infantile spasms. METHODS: Patients with video-electroencephalography (EEG) confirmed resolution of infantile spasms were retrospectively identified. Relevant clinical data were systematically collected, including lead time from onset of spasms to successful treatment response, etiology of infantile spasms, number of treatment failures prior to response, timing of relapse, and detailed exposure data for ZNS and TPM. RESULTS: We identified 106 patients with response to hormonal therapy (n = 58), vigabatrin (n = 25), or surgery (n = 23). To prevent relapse of infantile spasms, 37 patients received ZNS, 34 received TPM, 3 received both ZNS and TPM, and 38 patients received neither ZNS nor TPM. There were 44 relapses, occurring a median of 6.9 (3.2-10.8) months after initial response. Time to relapse was not affected by treatment with ZNS or TPM. Relapse was less likely among patients who were older (hazard ratio 0.97 [per month], p = 0.036) and those who responded to surgical resection (hazard ratio = 0.28, p = 0.017). Of note, we identified a relatively refractory cohort with multiple treatment failures and long lead time to initial response. SIGNIFICANCE: In this refractory cohort, neither ZNS nor TPM was successful in preventing relapse of infantile spasms, despite relatively high dosages. At this time, aside from surgical resection in eligible candidates, there is no known treatment that is efficacious in the prevention of relapse of infantile spasms.

A pulse rapamycin therapy for infantile spasms and associated cognitive decline.

Infantile spasms are seizures manifesting within a spectrum of epileptic encephalopathies of infancy that often lead to cognitive impairment. Their current therapies, including adrenocorticotropic hormone (ACTH), high dose steroids, or vigabatrin, are not always effective and may be associated with serious side effects. Overactivation of the TORC1 complex of the mTOR pathway is implicated in the pathogenesis of certain genetic and acquired disorders that are linked with infantile spasms, like tuberous sclerosis. Here, we tested the therapeutic potential of rapamycin, a TORC1 inhibitor, as a potential treatment for infantile spasms in the multiple-hit rat model of ACTH-refractory symptomatic infantile spasms, which is not linked to tuberous sclerosis. Rapamycin or vehicle was given after spasms appeared. Their effects on spasms, other seizures, performance in Barnes maze, and expression of the phosphorylated S6 ribosomal protein (pS6: a TORC1 target) in the cortex, using immunofluorescence, were compared. Rapamycin suppressed spasms dose-dependently and improved visuospatial learning, although it did not reduce the frequency of other emerging seizures. High-dose pulse rapamycin effected acute and sustained suppression of spasms and improved cognitive outcome, without significant side effects. Therapeutically effective rapamycin doses normalized the pS6 expression, which was increased in perilesional cortical regions of pups with spasms. These findings support that pathological overactivation of TORC1 may be implicated in the pathogenesis of infantile spasms, including those that are not linked to tuberous sclerosis. Furthermore, a high-dose, pulse rapamycin treatment is a promising, well tolerated and disease-modifying new therapy for infantile spasms, including those refractory to ACTH.

Infantile spasms and Down syndrome: a new animal model.

Infantile spasms is a catastrophic childhood seizure disorder for which few animal models exist. Children with Down syndrome are highly susceptible to infantile spasms. The Ts65Dn mouse is a valid model for Down syndrome; therefore, we tested the hypothesis that the Ts65Dn mouse represents a substrate for an animal model of infantile spasms. The baseline of naïve Ts65Dn mice showed spontaneous spike-and-wave discharges, a pattern that worsened with baclofen and gamma-butyrolactone, which induced acute epileptic extensor spasms (AEES) associated with epileptiform polyspike bursts and an electrodecremental response on the EEG. GABABR-agonist-induced AEES were significantly reduced with vigabatrin, rodent ACTH fragment, valproic acid, ethosuximide, and CGP 35348. Porcine ACTH had no effect. GABABR protein expression was significantly increased in the thalamus and medulla oblongata of Ts65D mice in comparison with wild-type controls. The GABABR agonist-treated Ts65Dn mouse shows the unique clinical, electrographic, and pharmacologic signature of infantile spasms and represents a valid, acute model of this disorder. GABABR-mediated mechanisms may contribute to the increased susceptibility of children with Down syndrome to infantile spasms.

Epilepsy development in infancy with epileptic discharges.

As a part of the study to prevent West syndrome (WS) by early treatment, we assessed what kind of epilepsy developed in infants who showed epileptic discharges in early infancy. EEG examinations were performed on 116 infants born from 1997 to September 2004, both before and after 3 months of corrected age (CA). We divided 45 infants who showed epileptic discharges in early infancy into two groups according to the existence of periventricular leukomalacia (PVL) and retrospectively performed the course observation at the survey point on April 1 in 2005. Out of 45 infants showing epileptic discharges in early infancy, 26 developed WS. Compared with infants without PVL, infants with PVL were more likely to develop WS than infants without PVL. Furthermore, infants with PVL were more likely to develop WS than other types of epilepsy. Namely, 11 out of 17 infants with PVL developed WS at the survey point. All infants with WS showed initial epileptic discharges before 5 months of corrected age (CA), and most of them (except for five) had initial epileptic discharges before 3 months of CA. There were two infants who once developed hypsarrhythmia on EEG; however, after starting VPA therapy, they did not develop WS with the improvement of EEG findings, and one was presented here in detail. We proposed that preterm infants with PVL who showed epileptic discharges before 3 months of CA should be treated by antiepileptic drugs to prevent the onset of WS syndrome.

[Aetiological aspects of West Syndrome].

INTRODUCTION: West Syndrome involves epileptic encephalopathy in infants, occurring with an incidence of 5/10000 live births. Its main clinical feature are spasms that occur in clusters, which are associated with an EEG pattern called hypsarrhythmia and psychomotor retardation in most patients. West Syndrome is associated with many underlying conditions and the terms idiopathic, cryptogenic, and symptomatic are used for its aetiological subgroups. OBJECTIVE: The objective of this investigation was to determine the aetiological diagnosis of patients with West Syndrome and to compare the results with other studies. METHOD: In this 34-year longitudinal prospective one-centre study, 404 patients were studied. All patients exhibiting the diagnostic criteria for West Syndrome were investigated by clinical and neurological examination, EEG, ophthalmologic, psychological, metabolic, genetic, as well as neuroradiological methods, according to their particular indications. RESULTS: 36 (8.9%) patients had normal development, in whom infantile spasms occurred without any identifiable underlying cause, forming the idiopathic group. 51 patients (12.6%) with neurological impairment of unknown aetiology formed the cryptogenic group. The greatest number of patients (317 or 78.5%) formed the symptomatic group, in which neurological features and developmental delay preceded the onset of spasms. Disgenetic disorders and hereditary metabolic diseases were aetiological factors 44 (10.8%) patients. Prenatal and perinatal aetiological factors were revealed in one third of the patients (134 or 31%). Postnatal aetiological factors were revealed in 42 (10.2%) patients. In our study, disgenetic disorders were registered less frequently and perinatal complications more frequently than in other studies. CONCLUSION: Our results indicate the possibility of preventing West Syndrome with good quality obstetric and neonatal care, as well as the early prenatal diagnosis of brain malformations. Modern, sophisticated investigation makes the more accurate aetiological diagnosis of West Syndrome possible.

Clobazam as add-on therapy in children with epileptic encephalopathy.

RATIONALE: Clobazam has been used successfully in adults and children with partial epilepsy. The purpose of this study was to evaluate the safety and efficacy of clobazam as add-on therapy in children with epileptic encephalopathy. METHODS: This was a retrospective study conducted at the pediatric epilepsy clinic of our university hospital. Children less than 18-years of age with epileptic encephalopathy were included in the study. Clobazam was introduced as add-on therapy, starting with 5 mg/Kg/day and increased in minimally effective doses, up to the maximum tolerated dose. Data were obtained from clinical files and follow-up visits. RESULTS: Ninety-seven patients were included in the study (39 girls), aged between 1 and 17-years-old (mean = 9.9). Twenty-six patients had Lennox-Gastaut syndrome, seven had myoclonic astatic epilepsy, nine had West syndrome and, in 57 patients, the type of epileptic encephalopathy could not be determined. Clobazam dosage ranged from 5 to 60 mg/day (mean = 37.5 mg/day). Forty (41%) patients presented with adverse events, most of which were mild and transitory, and clobazam needed to be withdrawn in only 11 patients. Nine (9.2%) patients were seizure-free after clobazam adjunctive therapy. In 11 (11.3%) patients seizure improvement was >75%, in 16 (16.5%) it was >50%, in 17 (17.5%) improvement was <50% and in 44 (45.5%) there was no change in seizure frequency. Three patients were lost to follow-up. In 85% of the patients with seizure improvement, the results lasted for more than one year. CONCLUSION: Clobazam is safe and effective in the treatment of epileptic encephalopathies of childhood.

Clinico-electrical evolution in pre-hypsarrhythmic stage: towards prediction and prevention of West syndrome.

We investigated serial electroencephalographic (EEG) changes before the onset of spasms in patients with West syndrome (WS) due to perinatal injury in order to determine whether one can predict WS or not. In preterm infants with periventricular leukomalacia (PVL), depression of EEG activities is commonly followed by disorganized pattern during the early neonatal period. Disorganized patterns persist until the late neonatal period, but epileptiform discharges do not appear. Epileptiform discharges usually appear during early infancy in infants who later develop WS. As the onset of WS was relatively later in preterm infants with PVL, it may be possible to select the patients at risk for secondary prevention of WS with sufficient treatment period. In term infants with hypoxic-ischemic encephalopathy, all EEGs during the neonatal period did not reveal epileptiform discharges in the majority of patients. Multifocal spikes were very likely to be observed during early infancy, but hypsarrhythmia was observed immediately after their appearance. It is not always easy to select patients for prevention of WS with sufficient treatment period.

[Early assessment in perinatal hypoxia. Prognostic markers]. / Evaluación precoz en la hipoxia perinatal. Marcadores pronósticos.

INTRODUCTION: Perinatal asphyxia and its neurological signs are the most important cause of brain damage and neurological sequelae in full term newborn babies. Neuroprotection treatments currently being investigated promise to reduce such sequelae, but these treatments are not without risk and the patients involved should be selected. OBJECTIVE: To analyze a scale composed of variables recorded from the start of delivery until the fourth hour of life, comparing the neurological evolution of the patients. By means of this scale we aim to establish a criterion for the selection of neonates with acute perinatal asphyxia, who would benefit from neuroprotector treatment. PATIENTS AND METHODS: A retrospective study was made of 50 patients with the diagnosis of perinatal asphyxia. Our scale was formed of the following variables: intrauterine meconiorrhexis, pathological cardiotocographic recordings, resuscitation at birth, Apgar score at five minutes, pH of the umbilical artery blood, neurological examination, multisystemic involvement, seizures, persistent metabolic acidosis and need for mechanical ventilation during the first hours of life. The patients were followed up for at least one year by means of periodical studies (neurological examination and evaluation of psychomotor development according to the Brunnet Lezinne test). For statistical analysis we used the chi squared test, Fisher's exact test, Kruskal-Wallis test and the area beneath the ROC curve. RESULTS AND CONCLUSIONS: The scale presented constitutes a rapid, easy method which is statistically significant for the selection of perinatal asphyxia of high neurological risk which would benefit from neuroprotector treatment after the event.

Age-specific N-methyl-D-aspartate-induced seizures: perspectives for the West syndrome model.

PURPOSE: With intraperitoneal N-methyl-D-aspartate (NMDA; 15-200 mg/kg) administration, we attempted to develop an animal model of age-specific West syndrome to serve for testing of putative anticonvulsant drugs and to determine the mechanisms of this disorder. METHODS: Experiments were performed in 12-, 18-, and 60-day-old (adult) rats. The effects of systemic pretreatment with hydrocortisone (5-25 mg/kg), pyridoxine (20-250 mg/kg), and sodium valproate (VPA; 200 and 400 mg/kg) against the NMDA-induced automatisms, emprosthotonic (hyperflexion), and clonic-tonic seizures were determined. NMDA-induced EEG changes and alterations of the performance in horizontal bar, rotorod, open field, and elevated plus-maze tests were recorded. RESULTS: In young rats, hydrocortisone had proconvulsant effects. High doses of pyridoxine induced epileptiform activity independent of and distinct from that induced by NMDA. Only VPA had moderate effects against the NMDA-induced syndrome. EEG consisted of periods of suppression mixed with ictal activity of serrated waves and high-voltage chaotic EEG activity. In adult rats, EEG alterations involved spike and spike-and-wave activity. NMDA also deteriorated performance of young rats in the open field, rotorod, and elevated plus maze tests. CONCLUSIONS: NMDA syndrome in rats fulfills some, but not all, criteria of the West syndrome model, such as occurrence of flexion seizures, nonspecific diffuse EEG changes, refractoriness to antiepileptic therapy (but a response to VPA), as well as long-term alteration of behavioral tasks. However, NMDA-induced seizures represent an acute model without the occurrence of spontaneous seizures, whereas in the clinical situation, both the seizures and neurologic deterioration are chronic. Further, in the West syndrome and the NMDA seizure model, there is an incongruent response to therapy with antiepileptic drugs.

Developmental outcomes in children receiving resection surgery for medically intractable infantile spasms.

Two-year postsurgical developmental outcomes were assessed in 24 children with infantile spasms who underwent resective surgery. The mean age of onset of infantile spasms was 12.0 weeks and the mean age at surgery was 20.8 months. Developmental outcomes were assessed using the Vineland Adaptive Behavior Scales (VABS). There was a significant increase in developmental level at 2 years postsurgery compared with presurgical levels. At 2 years postsurgery only one of the children in this series was severely retarded. The developmental outcomes of patients in the series were better than those in prior studies of symptomatic patients receiving medical treatment for infantile spasms. It is surprising that the children in the UCLA series frequently had developmental outcomes equal to and sometimes superior to other groups of children with infantile spasms, since all the UCLA patients were symptomatic, had neurologic deficits and had failed to respond to adrenocorticotrophic hormone (ACTH) and antiepileptic drugs. The 2-year postsurgery developmental outcomes were best for the children who received surgery when they were relatively young and who had the highest level of developmental attainments presurgically.

Low risk of seizure recurrence after early withdrawal of antiepileptic treatment in the neonatal period.

The risk of seizure recurrence within the first year of life was evaluated in infants with neonatal seizures diagnosed with a combination of clinical signs, amplitude-integrated electroencephalogram (EEG) monitoring, and standard EEG. Fifty eight of 283 (4.5%) neonates in tertiary level neonatal intensive care had seizures. The mortality in the infants with neonatal seizures was 36.2%. In 31 surviving infants antiepileptic treatment was discontinued after one to 65 days (median 4.5 days). Three infants received no antiepileptic treatment, two continued with prophylactic antiepileptic treatment. Seizure recurrence was present in only three cases (8.3%)--one infant receiving prophylaxis, one treated for 65 days, and in one infant treated for six days. Owing to the small number of infants with seizure recurrence, no clinical features could be specifically related to an increased risk of subsequent seizures. When administering antiepileptic treatment, one aim was to abolish both clinical and electrographical seizures. Another goal was to minimise the duration of treatment and to keep the treatment as short as possible. It is suggested that treating neonatal seizures in this way may not only reduce the risk of subsequent seizure recurrence, but may also minimise unnecessary non-specific prophylactic treatment for epilepsy.

Prognosis for seizure control in infantile spasms preceded by other seizures.

Thirteen to 43% of patients with infantile spasms (IS) have other types of seizures, which are considered a feature of an unfavourable prognosis and, to some extent, as a contra-indication for steroid treatment. The present series comprised 43 patients treated with steroids, who suffered from other types of seizures prior to IS. The first seizures resulted from 2 different conditions, correlated to a different outcome of epilepsy. In 27 patients with prenatal encephalopathy, the first seizures were the first manifestation of the epilepsy and IS responded poorly to steroids. In the other 16 patients, the first seizures were occasional, due to acute brain damage, and the following IS responded favourably to steroid therapy. Rational therapeutic indications should take in account the etiology of seizures that precedes IS, and steroids should be administered when IS are due to acute peri- or postnatal acute brain damage.

[Neuropsychiatric disorders in newborn infants with very low birth weight (VLBW infants)--before and following introduction of modern perinatal medicine. 2. Infantile cerebral palsy, epilepsy and mental handicap (oligophrenia)]. / Neuropsychiatrische Störungen bei Neugeborenen mit sehr niedrigem Geburtsgewicht (VLBW-infants)--vor und nach Einführung der modernen Perinatalmedizin. 2. Mitteilung: Infantile Cerebralparesen (ICP), Epilepsie und geistige Behinderungen (Oligophrenien).

Simultaneously with the introduction of modern perinatal intensive therapy the infantile cerebral palsies (ICP) of VLBW infants dropped on the average from 23 to 5.9 per cent. In Swedish and West-Australian ICP studies a considerable decrease in the ICP incidence was found in the 60's, but there was again a slight increase in the 70's. A decrease in the epilepsies was found on an average from 9 to 1.6 per cent, whereby in 10 of 16 actual studies mostly performed at early follow-up age no epilepsies were reported. A decrease in the mental retardations (oligophrenias) was found on an average from 22 to 10.6 per cent. There was especially noteworthy a reduction of the severe mental retardations from 8 to 10 per cent to an average of 2.3 per cent.