RESUMEN
OBJECTIVE: To report a prospectively planned analysis of two randomised controlled trials with embedded comparisons of prednisolone versus tetracosactide depot for the treatment of infantile epileptic spasms syndrome (IESS). METHODS: Individual patient data from patients randomly allocated to prednisolone or tetracosactide depot were analysed from two trials (UKISS, ICISS). The comparison was embedded within trials in which some patients also received vigabatrin but only patients receiving monotherapy with randomly allocated hormonal treatments are included in this analysis. The main outcome was cessation of spasms (Days 13-14 after randomisation). Lead time to treatment and underlying aetiology were taken into account. Cessation of spasms on Days 14-42 inclusive, electroclinical response (EEG Day 14), plus developmental and epilepsy outcomes (at 14 months in UKISS and 18 months in ICISS) are also reported. Minimum treatment was prednisolone 40 mg per day for two weeks or tetracosactide depot 0·5 mg IM on alternate days for two weeks, all followed by a reducing dose of prednisolone over two weeks. RESULTS: 126 infants were included in this study. On tetracosactide depot, 47 of 62 (76%) were free of spasms on Days 13-14 compared to 43 of 64 (67%) on prednisolone (difference 9%, 95% CI -7·2% to +25·2%, chi square 1·15, p = 0·28). For Day 14-42 cessation of spasms, on tetracosactide depot, 41 of 61 (67%) were free of spasms compared to 35 of 62 (56%) on prednisolone (difference 11%, 95% CI -6·4% to +28·4%, chi square 1·51, p = 0·22). There was no significant difference in mean VABS score between infants who received prednisolone compared with those who received tetracosactide depot (74·8 (SD 18·3) versus 78·0 (SD 20·2) t = -0·91 p = 0·36). The proportion with ongoing epilepsy at the time of developmental assessment was 20 of 61 (33%) in the tetracosactide group compared with 26 out of 63 (41%) in the prednisolone group (difference 8%, 95% CI -9·2% to +25·2%, Chi [2] 0·95, p = 0·33). SIGNIFICANCE: With hormone monotherapy, either prednisolone or tetracosactide depot may be recommended for infantile epileptic spasms syndrome.
Asunto(s)
Epilepsia , Espasmos Infantiles , Lactante , Humanos , Prednisolona/uso terapéutico , Cosintropina/uso terapéutico , Anticonvulsivantes/uso terapéutico , Espasmos Infantiles/tratamiento farmacológico , Vigabatrin/uso terapéutico , Epilepsia/tratamiento farmacológico , Síndrome , Espasmo , Resultado del Tratamiento , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
OBJECTIVE: To determine the underlying etiologies in a contemporary cohort of infants with infantile spasms and to examine response to treatment. METHODS: Identification of the underlying etiology and response to treatment in 377 infants enrolled in a clinical trial of the treatment of infantile spasms between 2007 and 2014 using a systematic review of history, examination, and investigations. They were classified using the pediatric adaptation of International Classification of Diseases, Tenth Revision (ICD-10). RESULTS: A total of 219 of 377 (58%) had a proven etiology, of whom 128 (58%) responded, 58 of 108 (54%) were allocated hormonal treatment, and 70 of 111 (63%) had combination therapy. Fourteen of 17 (82%, 95% confidence interval [CI] 59% to 94%) infants with stroke and infarct responded (compared to 114 of 202 for the rest of the proven etiology group (56%, 95% CI 48% to 62%, chi-square 4.3, P = .037): the better response remains when treatment allocation and lead time are taken into account (odds ratio 5.1, 95% CI 1.1 to 23.6, P = .037). Twenty of 37 (54%, 95% CI 38% to 70%) infants with Down syndrome had cessation of spasms compared to 108 of 182 (59%, 95% CI 52% to 66%, chi-square 0.35, P = .55) for the rest of the proven etiology group. The lack of a significant difference remains after taking treatment modality and lead-time into account (odds ratio 0.8, 95% CI 0.4 to 1.7, P = .62). In Down syndrome infants, treatment modality did not appear to affect response: 11 of 20 (55%) allocated hormonal therapy responded, compared to 9 of 17 (53%) allocated combination therapy. SIGNIFICANCE: This classification allows easy comparison with other classifications and with our earlier reports. Stroke and infarct have a better outcome than other etiologies, whereas Down syndrome might not respond to the addition of vigabatrin to hormonal treatment.
Asunto(s)
Malformaciones del Desarrollo Cortical/complicaciones , Espasmos Infantiles/etiología , Accidente Cerebrovascular/complicaciones , Anticonvulsivantes/uso terapéutico , Femenino , Humanos , Lactante , Masculino , Malformaciones del Desarrollo Cortical/fisiopatología , Prednisolona/uso terapéutico , Espasmos Infantiles/tratamiento farmacológico , Espasmos Infantiles/fisiopatología , Accidente Cerebrovascular/fisiopatología , Vigabatrin/uso terapéuticoRESUMEN
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.
Asunto(s)
Cosintropina/uso terapéutico , Prednisolona/uso terapéutico , Espasmos Infantiles/tratamiento farmacológico , Vigabatrin/uso terapéutico , Cosintropina/administración & dosificación , Esquema de Medicación , Quimioterapia Combinada , Electroencefalografía , Femenino , Humanos , Lactante , Masculino , Prednisolona/administración & dosificación , Espasmos Infantiles/prevención & control , Vigabatrin/administración & dosificaciónRESUMEN
BACKGROUND: Infantile spasms constitutes a severe infantile epilepsy syndrome that is difficult to treat and has a high morbidity. Hormonal therapies or vigabatrin are the most commonly used treatments. We aimed to assess whether combining the treatments would be more effective than hormonal therapy alone. METHODS: In this multicentre, open-label randomised trial, 102 hospitals (Australia [three], Germany [11], New Zealand [two], Switzerland [three], and the UK [83]) enrolled infants who had a clinical diagnosis of infantile spasms and a hypsarrhythmic (or similar) 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 electro-clinical outcome were masked to treatment allocation. Minimum doses were prednisolone 10 mg four times a day or intramuscular tetracosactide depot 0·5 mg (40 IU) on alternate days with or without vigabatrin 100 mg/kg per day. The primary outcome was cessation of spasms, which was defined as no witnessed spasms on and between day 14 and day 42 from trial entry, as recorded by parents and carers in a seizure diary. Analysis was by intention to treat. The trial is registered with The International Standard Randomised Controlled Trial Number (ISRCTN), number 54363174, and the European Union Drug Regulating Authorities Clinical Trials (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 (186) or hormonal therapy alone (191). All 377 infants were assessed for the primary outcome. Between days 14 and 42 inclusive no spasms were witnessed in 133 (72%) of 186 patients on hormonal therapy with vigabatrin compared with 108 (57%) of 191 patients on hormonal therapy alone (difference 15·0%, 95% CI 5·1-24·9, p=0·002). Serious adverse reactions necessitating hospitalisation occurred in 33 infants (16 on hormonal therapy alone and 17 on hormonal therapy with vigabatrin). The most common serious adverse reaction was infection occurring in five infants on hormonal therapy alone and four on hormonal therapy with vigabatrin. There were no deaths attributable to treatment. INTERPRETATION: Hormonal therapy with vigabatrin is significantly more effective at stopping infantile spasms than hormonal therapy alone. The 4 week period of spasm cessation required to achieve a primary clinical response to treatment suggests that the effect seen might be sustained, but this needs to be confirmed at the 18 month follow-up. FUNDING: The Castang Foundation, Bath Unit for Research in Paediatrics, National Institute of Health Research, the Royal United Hospitals Bath NHS Foundation Trust, the BRONNER-BENDUNG Stifung/Gernsbach, and University Children's Hospital Zurich.
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Anticonvulsivantes/uso terapéutico , Hormonas/uso terapéutico , Espasmos Infantiles/tratamiento farmacológico , Resultado del Tratamiento , Vigabatrin/uso terapéutico , Cosintropina/uso terapéutico , Esquema de Medicación , Quimioterapia Combinada , Electroencefalografía , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Prednisolona/uso terapéuticoAsunto(s)
Convulsiones Febriles/diagnóstico , Antipiréticos/uso terapéutico , Benzodiazepinas/uso terapéutico , Manejo de la Enfermedad , Epilepsia/diagnóstico , Humanos , Recurrencia , Factores de Riesgo , Convulsiones Febriles/clasificación , Convulsiones Febriles/tratamiento farmacológico , Convulsiones Febriles/etiologíaRESUMEN
We report on a large family with myoclonus-dystonia resulting from an epsilon-sarcoglycan mutation, with prominent early and late lower-limb involvement. The proband's condition has evolved to include marked lower-limb dystonia and dystonic gait impairment in the fourth decade. Other family members had evidence of prominent lower-limb involvement at presentation or a more typical phenotype of axial and upper-limb myoclonus and dystonia. Prominent lower-limb involvement developing late in the disease course is an atypical feature and exemplifies the wide phenotypic heterogeneity observed in people with myoclonus-dystonia.
RESUMEN
AIM: We aimed to investigate the relationship between movement disorders, changes on brain magnetic resonance imaging (MRI), and vigabatrin therapy in children with infantile spasms. METHOD: Retrospective review and brain MRI analysis of children enrolled in the International Collaborative Infantile Spasms Study (ICISS) who developed a movement disorder on vigabatrin therapy. Comparisons were made with controls within ICISS who had no movement disorder. RESULTS: Ten of 124 infants had a movement disorder and in eight it had developed on vigabatrin therapy. Two had a movement disorder that resolved on dose-reduction of vigabatrin, one had improvement on withdrawing vigabatrin, two had resolution without any dose change, and in three it persisted despite vigabatrin withdrawal. The typical brain MRI changes associated with vigabatrin therapy were noted in two infants. Ten control infants were identified. Typical MRI changes noted with vigabatrin were noted in three controls. INTERPRETATION: It is possible that in two out of eight cases, vigabatrin was associated with the development of a movement disorder. In six out of eight cases a causal relationship was less plausible. The majority of infants treated with vigabatrin did not develop a movement disorder. MRI changes associated with vigabatrin do not appear to be specifically related to the movement disorder.
Asunto(s)
Anticonvulsivantes/efectos adversos , Encéfalo/patología , Trastornos del Movimiento/etiología , Espasmos Infantiles/complicaciones , Espasmos Infantiles/tratamiento farmacológico , Vigabatrin/efectos adversos , Anticonvulsivantes/administración & dosificación , Ganglios Basales/patología , Encéfalo/efectos de los fármacos , Tronco Encefálico/patología , Cerebelo/patología , Femenino , Globo Pálido/patología , Humanos , Lactante , Imagen por Resonancia Magnética , Masculino , Trastornos del Movimiento/patología , Estudios Retrospectivos , Espasmos Infantiles/patología , Vigabatrin/administración & dosificaciónRESUMEN
PURPOSE: The ILAE recommends baseline recordings of 30 min to detect abnormalities supporting a clinical diagnosis of epilepsy in children. A shorter recording time may be better tolerated by children and be more resource-efficient. Our aim was to determine how many abnormalities supporting a diagnosis of epilepsy would be missed by reducing the recording time of paediatric standard electroencephalograms (EEGs) from 20 to 15 min. METHODS: We evaluated standard EEGs of 300 patients aged 2 months to 17 years referred consecutively with confirmed or suspected epilepsy. EEGs were recorded for 20 min on digital media. A digital copy of each EEG was truncated to give consecutive sequences of 10 min (sequence "A") and 5 min duration (sequences "B" and "C" respectively). A panel of EEG raters blinded to the children's' details other than age identified these sequences as "normal" or "abnormal" if they contained spike waves, discrete sharp waves or notched slow waves in the respective EEG period. RESULTS: EEGs of 297 children were analysed (three were omitted for technical reasons). 109 out of 297 EEGs (37%) had specific abnormalities supportive of a diagnosis of an epilepsy. 17 of these EEGs showed the abnormality in EEG sequences "B" or "C" and 7 (95% CI: 1.9-12.2) out of these demonstrated the abnormality in sequence "C" only. 105 out of 297 EEGs had non-specific findings. CONCLUSION: We conclude that reducing the recording time of standard EEGs to 15 min may miss abnormalities in 2.36% [95% CI: 0.63-4.09%] overall and 6.42% [95% CI: 2.2-11.8%] of those with an abnormality supportive of an epilepsy to explain the reported symptoms. This result should inform any future discussions on seeking resource-efficiencies.
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Electroencefalografía/métodos , Epilepsia/diagnóstico , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , TiempoRESUMEN
PURPOSE: Infantile spasms is a severe infantile seizure disorder. Several factors affect developmental outcome, especially the underlying etiology of the spasms. Treatment also affects outcome. Both age at onset of spasms and lead time to treatment (the time from onset of spasms to start of treatment) may be important. We investigated these factors. METHODS: Developmental assessment using Vineland Adaptive Behaviour Scales (VABS) at 4 years of age in infants enrolled in the United Kingdom Infantile Spasms Study. Date of or age at onset of spasms was obtained prospectively. Lead time to treatment was then categorized into five categories. The effects of lead time to treatment, age of onset of spasms, etiology, and treatment on developmental outcome were investigated using multiple linear regression. KEY FINDINGS: Age of onset ranged (77 infants) from <1 to 10 months (mean 5.2, standard deviation 2.1). Lead time to treatment was 7 days or less in 11, 8-14 days in 16, 15 days to 1 month in 8, 1-2 months in 15, >2 months in 21 and not known in 6. Each month of reduction in age at onset of spasms was associated with a 3.1 [95% confidence interval (CI) 0.64-5.5, p = 0.03] decrease, and each increase in category of lead time duration associated with a 3.9 (95% CI 7.3-0.4, p = 0.014) decrease in VABS, respectively. There was a significant interaction between treatment allocation and etiology with the benefit in VABS in those allocated steroid therapy being in children with no identified etiology (coefficient 29.9, p=0.004). SIGNIFICANCE: Both prompt diagnosis and prompt treatment of infantile spasms may help prevent subsequent developmental delay. Younger infants may be more at risk from the epileptic encephalopathy than older infants.
Asunto(s)
Desarrollo Infantil , Espasmos Infantiles/diagnóstico , Edad de Inicio , Anticonvulsivantes/uso terapéutico , Desarrollo Infantil/efectos de los fármacos , Desarrollo Infantil/fisiología , Cosintropina/uso terapéutico , Diagnóstico Precoz , Humanos , Lactante , Recién Nacido , Modelos Lineales , Prednisolona/uso terapéutico , Pronóstico , Espasmos Infantiles/tratamiento farmacológico , Espasmos Infantiles/etiología , Espasmos Infantiles/fisiopatología , Reino Unido , Vigabatrin/uso terapéuticoRESUMEN
PURPOSE: To examine the underlying etiology of infantile spasms from the United Kingdom Infantile Spasms Study (UKISS), using the pediatric adaptation of ICD 10. METHODS: Infants were enrolled in a randomized controlled trial or a parallel epidemiologic study. Etiological information included history, examination, and investigations. The infants were classified as proven etiology, if a neurologic disease was identified; as no identified etiology, if no neurologic disease was identified; and as not fully investigated, if a major piece of information was missing. Proven etiology was subclassified using the pediatric adaptation of ICD 10. The results were then examined to identify further methods of classification. RESULTS: Of 207 infants, 127 (61%) had proven etiology, 68 (33%) had no identified etiology, and 12 (6%) were not fully investigated. Etiologies were prenatal in 63, perinatal in 38, postnatal in 8, and 18 other. The most common etiologies were: hypoxic-ischemic encephalopathy (HIE) 21 (10%), chromosomal 16 (8%), malformations 16 (8%), stroke 16 (8%), tuberous sclerosis complex (TSC) 15 (7%), and periventricular leukomalacia or hemorrhage 11 (5%). The remaining 32 etiologies were all individually uncommon. Response to treatment is given for individual etiologies. DISCUSSION: Our method of classification allows the reporting of results by individual diseases, disease groups, or categories and is structured and clear. It avoids the use of poorly defined terms such as symptomatic and cryptogenic. It can adapt to new neurologic diseases, such as gene defects, and can be used for comparison of different groups of infants, thereby aiding meta-analysis.
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Enfermedades del Sistema Nervioso/clasificación , Enfermedades del Sistema Nervioso/diagnóstico , Espasmos Infantiles/diagnóstico , Espasmos Infantiles/etiología , Femenino , Humanos , Hipoxia-Isquemia Encefálica/complicaciones , Hipoxia-Isquemia Encefálica/diagnóstico , Lactante , Recién Nacido , Clasificación Internacional de Enfermedades/estadística & datos numéricos , Masculino , Estudios Multicéntricos como Asunto , Enfermedades del Sistema Nervioso/complicaciones , Malformaciones del Sistema Nervioso/complicaciones , Malformaciones del Sistema Nervioso/diagnóstico , Embarazo , Diagnóstico Prenatal , Ensayos Clínicos Controlados Aleatorios como Asunto/estadística & datos numéricos , Espasmos Infantiles/epidemiología , Terminología como Asunto , Resultado del Tratamiento , Esclerosis Tuberosa/complicaciones , Esclerosis Tuberosa/diagnóstico , Reino Unido/epidemiologíaRESUMEN
BACKGROUND: Infantile spasms is the name given to a difficult to treat, severe infantile epilepsy with high morbidity. The United Kingdom Infantile Spasms Study (UKISS) showed that absence of spasms on days 13 and 14 after randomisation was more common in infants allocated hormonal treatments than vigabatrin. At 12-14 months, those with no identified aetiology allocated hormonal treatment had better development. However, epilepsy outcome was not affected by treatment allocated. It is not known if the difference in development persists as the infants grow. METHODS: Infants in UKISS were followed up blind to treatment allocation by telephone at a mean age of 4 years using the Vineland Adaptive Behaviour Scales (VABS) and an epilepsy questionnaire. FINDINGS: 9 of 107 enrolled infants had died. 77 were traced and consented to take part. The median (quartile) VABS scores were 60 (42, 97) for the 39 allocated hormonal treatment and 50 (36, 67) for the 38 allocated vigabatrin (Mann-Whitney U=575; p=0.091; median difference (95% CI): 8 (-1 to 19)). For those with no identified aetiology, VABS scores were 96 (52, 102) for the 21 allocated hormonal treatment and 63 (37, 92) for the 16 allocated vigabatrin (U=98.5; p=0.033; median difference (95% CI): 14 (1 to 42)).The proportions in each treatment group with epilepsy were similar. INTERPRETATION: For all 77 infants, development and epilepsy outcomes were not significantly different between the two treatment groups. The better development seen at 14 months in those with no identified aetiology allocated hormonal treatment was seen again at 4 years in this study.
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Anticonvulsivantes/uso terapéutico , Glucocorticoides/uso terapéutico , Espasmos Infantiles/tratamiento farmacológico , Vigabatrin/uso terapéutico , Desarrollo Infantil/efectos de los fármacos , Preescolar , Cosintropina/uso terapéutico , Métodos Epidemiológicos , Humanos , Lactante , Prednisolona/uso terapéutico , Índice de Severidad de la Enfermedad , Espasmos Infantiles/psicología , Resultado del TratamientoRESUMEN
The chickenpox virus (varicella zoster virus; VZV) is known to cause large and small vessel central nervous system vasculopathies that may be associated with strokes in both adults and children. We present the case of a female aged 2 years 6 months who developed a chronic progressive small-vessel vasculopathy with radiological features of moyamoya disease as a manifestation of congenital varicella syndrome. Clinically, the condition was characterized by recurrent ischaemic strokes, which were brought under control using intravenous acyclovir. The case is unique in that it is the first report of congenital varicella syndrome to occur after a maternal herpes zoster infection. Furthermore, it is the first case of symptomatic VZV infection in a child to occur after a maternal infection occurring in the third trimester of pregnancy.
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Hemiplejía/etiología , Herpes Zóster/congénito , Complicaciones Infecciosas del Embarazo , Accidente Cerebrovascular/virología , Adulto , Preescolar , Femenino , Humanos , Embarazo , Tercer Trimestre del Embarazo , RecurrenciaRESUMEN
This study examined children with an acute encephalopathy illness for evidence of viral infection, disordered blood-brain barrier function, intrathecal immunoglobulin synthesis, and interferon (IFN) production, and related their temporal occurrence to outcome. A prospective study of 22 children (13 males, 9 females; age range 1mo to 13y, median 2y 4mo), recorded clinical details, with serum and cerebrospinal fluid (CSF) analysis near presentation and then on convalescent specimens taken up to day 39 of the neurological illness. Outcome was assessed with standard scales between 18 months and 3 years after presentation. A history consistent with viral infection was given in 17 children but laboratory evidence of viral infection was found in only 7 (7/17). In 18 out of 21 children, an elevated CSF:serum albumin ratio indicative of impairment of the blood-CSF and blood-brain barriers was detected at some stage of the illness. In 14 of the 15 children with a raised immunoglobulin G index, and in 12 of the 14 children where the CSF was positive for oligoclonal bands, this was preceded by, or was observed at the same time as, an abnormal albumin ratio. Sixteen children (16/18) had elevated IFN-alpha levels in serum, or CSF, or in both. We conclude that these findings indicate an initial disruption of the blood-brain barrier followed by intrathecal antibody production by activated lymphocytes, clonally restricted to a few antigens. This is the first in vivo study to show this as an important pathogenetic mechanism of encephalitis in children. Poor outcome was associated with young age, a deteriorating electroencephalogram pattern from grade 1 to grade 2, and the degree of blood-brain barrier impairment, particularly when prolonged, but not with Glasgow Coma Scale score. The persistence of IFN-alpha was associated with a good prognosis.
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Enfermedades Virales del Sistema Nervioso Central/tratamiento farmacológico , Enfermedades Virales del Sistema Nervioso Central/inmunología , Enfermedad Aguda , Adolescente , Albúminas/líquido cefalorraquídeo , Barrera Hematoencefálica/fisiología , Enfermedades Virales del Sistema Nervioso Central/fisiopatología , Enfermedades Virales del Sistema Nervioso Central/virología , Niño , Preescolar , Coma/epidemiología , Electroencefalografía , Femenino , Escala de Coma de Glasgow , Humanos , Inmunoglobulina G/líquido cefalorraquídeo , Inmunoglobulina G/inmunología , Lactante , Recién Nacido , Interferón-alfa/líquido cefalorraquídeo , Masculino , Bandas Oligoclonales/líquido cefalorraquídeo , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Virosis/líquido cefalorraquídeo , Virosis/inmunología , Virosis/virologíaRESUMEN
This case series describes four children who had meningitis in the neonatal period. After a stable period of years, they developed a myelopathy caused by chronic arachnoiditis. The myelopathy was precipitated by a fall in two cases, and in two cases there was an acute deterioration after surgery. A history of neonatal meningitis should be taken into consideration before planning surgery or anaesthesia. Careful intra-operative positioning, immobilisation of the neck, and maintenance of blood pressure is important but may not prevent this complication.
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Aracnoiditis/etiología , Meningitis Bacterianas/complicaciones , Enfermedades de la Médula Espinal/etiología , Adolescente , Aracnoiditis/patología , Aracnoiditis/cirugía , Resultado Fatal , Femenino , Humanos , Hidrocefalia/complicaciones , Hidrocefalia/patología , Recién Nacido , Imagen por Resonancia Magnética , Masculino , Meningitis por Escherichia coli/complicaciones , Meningitis por Escherichia coli/patología , Meningitis Neumocócica/complicaciones , Meningitis Neumocócica/patología , Procedimientos Neuroquirúrgicos , Médula Espinal/patología , Enfermedades de la Médula Espinal/patología , Enfermedades de la Médula Espinal/cirugía , Tomografía Computarizada por Rayos X , Derivación VentriculoperitonealRESUMEN
BACKGROUND: Infantile spasms is a severe infantile seizure disorder that is difficult to treat and has a high morbidity. Absence of spasms on days 13 and 14 after randomisation is more common in infants allocated hormone treatments than in those allocated vigabatrin. We sought to assess whether early control of spasms is associated with improved developmental or epilepsy outcomes. METHODS: Infants enrolled in the United Kingdom Infantile Spasms Study (UKISS) were randomly assigned hormone treatment (n=55) or vigabatrin (n=52) and were followed up until clinical assessment at 12-14 months of age. We assessed neurodevelopment with the Vineland adaptive behaviour scales (VABS) at 14 months of age on an intention to treat basis. FINDINGS: Of 107 infants enrolled, five died and 101 survivors reached both follow-up assessments. Absence of spasms at final clinical assessment (hormone 41/55 [75%] vs vigabatrin 39/51 [76%]) was similar in each treatment group (difference 1.9%, 95% CI -18.3% to 14.4%; chi(2)=0.05; p=0.82). Mean VABS score did not differ significantly (hormone 78.6 [SD 16.8] vs vigabatrin 77.5 [SD 12.7]; difference 1.0, 95% CI -4.9 to 7.0; t(99)=0.35, p=0.73). In infants with no identified underlying aetiology, the mean VABS score was higher in those allocated hormone treatment than in those allocated vigabatrin (88.2 [17.3] vs 78.9 [14.3]; difference 9.3, 95% CI 1.2 to 17.3; t(95)=2.28, p=0.025). INTERPRETATION: Hormone treatment controls spasms better than does vigabatrin initially, but not at 12-14 months of age. Better initial control of spasms by hormone treatment in those with no identified underlying aetiology may lead to improved developmental outcome.
Asunto(s)
Antiinflamatorios/uso terapéutico , Anticonvulsivantes/uso terapéutico , Cosintropina/uso terapéutico , Epilepsia/tratamiento farmacológico , Prednisolona/uso terapéutico , Espasmos Infantiles/tratamiento farmacológico , Vigabatrin/uso terapéutico , Adaptación Psicológica/fisiología , Anticonvulsivantes/efectos adversos , Desarrollo Infantil , Progresión de la Enfermedad , Epilepsia/epidemiología , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Prevención Secundaria , Espasmos Infantiles/epidemiología , Resultado del Tratamiento , Reino Unido/epidemiología , Vigabatrin/efectos adversosAsunto(s)
Anticonvulsivantes/uso terapéutico , Epilepsia/tratamiento farmacológico , Guías de Práctica Clínica como Asunto/normas , Anticonvulsivantes/efectos adversos , Ensayos Clínicos como Asunto/normas , Epilepsia/clasificación , Epilepsia/diagnóstico , Medicina Basada en la Evidencia , Humanos , Terminología como Asunto , Resultado del TratamientoRESUMEN
BACKGROUND: Infantile spasms, which comprise a severe infantile seizure disorder, have a high morbidity and are difficult to treat. Hormonal treatments (adrenocorticotropic hormone and prednisolone) have been the main therapy for decades, although little evidence supports their use. Vigabatrin has been recorded to have a beneficial effect in this disorder. We aimed to compare the effects of vigabatrin with those of prednisolone and tetracosactide in the treatment of infantile spasms. METHODS: The United Kingdom Infantile Spasms Study assessed these treatments in a multicentre, randomised controlled trial in 150 hospitals in the UK. The primary outcome was cessation of spasms on days 13 and 14. Minimum doses were vigabatrin 100 mg/kg per day, oral prednisolone 40 mg per day, or intramuscular tetracosactide depot 0.5 mg (40 IU) on alternate days. Analysis was by intention to treat. FINDINGS: Of 208 infants screened and assessed, 107 were randomly assigned to vigabatrin (n=52) or hormonal treatments (prednisolone n=30, tetracosactide n=25). None was lost to follow-up. Proportions with no spasms on days 13 and 14 were: 40 (73%) of 55 infants assigned hormonal treatments (prednisolone 21/30 [70%], tetracosactide 19/25 [76%]) and 28 (54%) of 52 infants assigned vigabatrin (difference 19%, 95% CI 1%-36%, p=0.043). Two infants allocated tetracosactide and one allocated vigabatrin received prednisolone. Adverse events were reported in 30 (55%) of 55 infants on hormonal treatments and 28 (54%) of 52 infants on vigabatrin. No deaths were recorded. INTERPRETATION: Cessation of spasms was more likely in infants given hormonal treatments than those given vigabatrin. Adverse events were common with both treatments.