United Kingdom Infantile Spasms Study Research Articles

Response to sequential treatment with prednisolone and vigabatrin in infantile spasms.

To report response to first treatment in infants with infantile spasms (IS), including incremental benefit of prednisolone 60 mg/day and vigabatrin following prednisolone 40 mg/day failure in infants commenced on the United Kingdom Infantile Spasms Study (UKISS) treatment sequence. In this retrospective analysis, we compared effectiveness of prednisolone, vigabatrin and nonstandard treatments as first treatment for IS. In infants who commenced the UKISS treatment sequence, we evaluated response to each step. Primary outcome was spasm cessation after 42 days. Secondary outcomes were severe side effects and spasm relapse after 42 days. Treatment response data were available for 151 infants. First treatment was prednisolone in 99 infants, vigabatrin in 18 and nonstandard treatment in 34. The rate of spasm cessation with first treatment was significantly higher with prednisolone (62/99, 63%) than vigabatrin (5/18, 28%, P= 0.01) or nonstandard treatment (2/34, 5.9%, P< 0.01). Of 112 infants who commenced the UKISS treatment sequence, 71/112 (63%) responded to prednisolone 40 mg/day. Among non-responders, 12/29 (41%) subsequently responded to prednisolone 60 mg/day, and 10/22 (45%) to vigabatrin. Severe side effects and spasm relapse were not significantly different between each treatment. We confirm higher rates of spasm cessation with initial treatment with prednisolone than vigabatrin and nonstandard therapy. Non-use of prednisolone as first treatment in over one third of infants highlights a concerning treatment gap. The UKISS treatment sequence has high overall treatment response (total 93/112; 83%), with similar benefit of subsequent prednisolone 60 mg/day and vigabatrin in prednisolone 40 mg/day non-responders.

Clinical profile, treatment modalities, and outcomes in patients with infantile spasms: A retrospective study from the United Arab of Emirates (UAE)

BackgroundInfantile spasms (IS) are an epileptic encephalopathy where the prognosis is generally poor, with most patients exhibiting psychomotor retardation or intractable epilepsy. However, it is claimed that early and aggressive treatment is related to better response rate and outcome, especially in patients with idiopathic IS. ObjectiveTo investigate different treatment modalities and outcomes in patients with IS attending a pediatric neurology clinic at a specialized neurology center in Abu Dhabi, United Arab Emirates. MethodsRetrospective chart review was done for detailed history, demographic data, etiology, neuro-diagnostic workup, treatment modalities, and the outcomes for all patients diagnosed with IS from September 2014 to September 2019. ResultsThree treatment modalities were identified as 1st line- Prednisolone United Kingdom Infantile Spasms Study (UKISS) (N = 15, 46.8%), Anti-Seizure Medications (ASMs) (N = 12, 37.5%), and Vigabatrin (N = 5, 15.6%). The complete response rate to Vigabatrin as a 1st line treatment showed the highest statistical significance (X2 = 7.34, p = 0.007). Patients with idiopathic IS showed a comparable response to treatment to those with symptomatic IS. Additional response to 2nd line treatment with Prednisolone UKISS protocol (25%) and Vigabatrin (15%) was noted in patients who showed partial or no response to the 1st line treatment. None of our patients received Adrenocorticotropic Hormone as treatment. All patients with desirable final outcomes were with idiopathic IS and none were symptomatic. ConclusionMore than a third of our patients showed poor treatment response whenever they were not offered treatment according to the current available protocols. This indicates an urgent need for having a unified treatment protocol that takes into consideration the availability of medications, professional expertise as well as diagnostic workup outside major tertiary care centers in our region.

Erratum: Association of Child Neurology (AOCN) — Indian Epilepsy Society (IES) Consensus Guidelines for the Diagnosis and Management of West Syndrome

The first sentence of last paragraph, column 1, page 61 should read: “In the 2004 United Kingdom Infantile Spasms study, spasm freedom was achieved in 70% of children taking high dose oral prednisolone (40–60 mg/day) and 76% of children taking ACTH (40 IU/alternate day) [21]” instead of “In the 2004 United Kingdom Infantile Spasms study, spasm freedom was achieved in 70% of children taking high dose oral prednisolone (40–60 mg/kg/day) and 76% of children taking ACTH (40 IU/alternate day) [21].”

Outcomes of High-Dose Steroid Therapy for Infantile Spasms in Children With Trisomy 21.

We performed a retrospective chart review of patients with trisomy 21 and infantile spasms in our university-based pediatric epilepsy center between 2002 and 2016 in order to describe the clinical characteristics of children with these diagnoses as well as to evaluate their response to first-line treatments. Patients with infantile spasms were identified via the neurophysiology database. Charts were reviewed with attention to infantile spasms diagnosis, presence of trisomy 21, age of reported clinical onset, treatment lag, treatments used, response to treatment, imaging findings, electroencephalography (EEG) data, and developmental outcomes. Of the 310 patients with infantile spasms, 24 also had trisomy 21. Three patients did not meet inclusion criteria. Ten of the 21 patients received nonstandard therapies first line; 2 of the 10 (20%) achieved spasm control, and 4 of the 8 who failed therapy (50%) progressed to Lennox-Gastaut syndrome. Eleven of the 21 patients received standard therapies as first-line treatments (10 with prednisolone according to the protocol in the United Kingdom Infantile Spasms Study [UKISS] and 1 with adrenocorticotrophic hormone [ACTH]). Nine of the 10 patients (90%) who received prednisolone achieved spasm resolution, 6 (60%) of these without relapse. The final patient (10%) failed prednisolone as well as ACTH. One patient received ACTH first line with success. This is the only series to follow children with trisomy 21 and infantile spasms in which a significant proportion received UKISS-protocol prednisolone. It adds to current knowledge about safety, tolerability, and effectiveness of prednisolone in this group.

Local Experience in using Hormonal Therapies according to the UKISS Studies in the Treatment of Infantile Spasms in Hong Kong

AbstractInfantile spasms constitute severe epileptic encephalopathy in infancy with characteristic seizure semiology and electroencephalographic patterns. Besides the spasms, the most detrimental effect is the impact on future developmental outcomes. Different treatment methods are used, but hormonal therapy is the most well-accepted method for treating infantile spasms in nontuberous sclerosis cases. After the launch of the original United Kingdom Infantile Spasms Study (UKISS) and the two follow-up articles, the regimens of hormonal therapy became more structured and the expected treatment outcomes were studied better. We would like to share our local experience using this protocol to treat patients with infantile spasms in Hong Kong with a case series of four patients.

SLC39A8 Deficiency: A Disorder of Manganese Transport and Glycosylation

SLC39A8 is a membrane transporter responsible for manganese uptake into the cell. Via whole-exome sequencing, we studied a child that presented with cranial asymmetry, severe infantile spasms with hypsarrhythmia, and dysproportionate dwarfism. Analysis of transferrin glycosylation revealed severe dysglycosylation corresponding to a type II congenital disorder of glycosylation (CDG) and the blood manganese levels were below the detection limit. The variants c.112G>C (p.Gly38Arg) and c.1019T>A (p.Ile340Asn) were identified in SLC39A8. A second individual with the variants c.97G>A (p.Val33Met) and c.1004G>C (p.Ser335Thr) on the paternal allele and c.610G>T (p.Gly204Cys) on the maternal allele was identified among a group of unresolved case subjects with CDG. These data demonstrate that variants in SLC39A8 impair the function of manganese-dependent enzymes, most notably β-1,4-galactosyltransferase, a Golgi enzyme essential for biosynthesis of the carbohydrate part of glycoproteins. Impaired galactosylation leads to a severe disorder with deformed skull, severe seizures, short limbs, profound psychomotor retardation, and hearing loss. Oral galactose supplementation is a treatment option and results in complete normalization of glycosylation. SLC39A8 deficiency links a trace element deficiency with inherited glycosylation disorders.

The effect of lead time to treatment and of age of onset on developmental outcome at 4 years in infantile spasms: Evidence from the United Kingdom Infantile Spasms Study

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. 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. 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). 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.

Seizure outcome in infantile spasms—A retrospective study

Prior to the United Kingdom Infantile Spasms Study (UKISS), our practice was to initiate vigabatrin for infantile spasms. However, since then we tend to use steroids as first-line agent for infantile spasms. Herein we compare seizure-free outcomes in children with infantile spasms on steroid therapy or vigabatrin therapy. This was a retrospective case study over 8 years of children with infantile spasms who were treated at our center. A positive response to therapy was defined as a two-week spasm-free interval. Of the 98 children presenting to us, 75 were included for this study. The ratio of cryptogenic to symptomatic spasms was 24:51. The response rate for steroid therapy was 61.1% and 42.5% for vigabatrin. Cessation of spasms was achieved faster in the group receiving steroids. Both groups had similar relapse rates. Steroids had significantly better response in the cryptogenic group, whereas in the symptomatic group both the medications were equally effective. Cryptogenic spasms have a better neurodevelopmental outcome. Early introduction of therapy for spasms did not predict a good neurodevelopmental outcome. Seventy-eight percent of children with spasms had seizures of other types at 12 months follow-up. At our center, steroids are now the preferred choice for initial therapy of infantile spasms. This is likely to have been a beneficial change, particularly for children with cryptogenic spasms. Spasms in 25% of the patients tend to be refractory, and the majority of patients from the cohort continue to have epilepsy with motor and cognitive disabilities.

The underlying etiology of infantile spasms (West syndrome): Information from the United Kingdom Infantile Spasms Study (UKISS) on contemporary causes and their classification2

To examine the underlying etiology of infantile spasms from the United Kingdom Infantile Spasms Study (UKISS), using the pediatric adaptation of ICD 10. 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. 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. 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.

Developmental and epilepsy outcomes at age 4 years in the UKISS trial comparing hormonal treatments to vigabatrin for infantile spasms: a multi-centre randomised trial

BackgroundInfantile 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...

P201 The aetiology of infantile spasms: information from the United Kingdom Infantile Spasms Study (UKISS) using an adaptation of the paediatric classification from ICD 10

P201 The aetiology of infantile spasms: information from the United Kingdom Infantile Spasms Study (UKISS) using an adaptation of the paediatric classification from ICD 10

High-dose oral prednisolone for infantile spasms: An effective and less expensive alternative to ACTH

The ideal treatment of infantile spasms is unclear, but many studies advocate hormonal treatment. In the United States, intramuscular ACTH is most widely used, despite the problematic financial cost and side effect profile. Since September 2007, we have replaced ACTH with high-dose oral prednisolone (40-60 mg/day) according to the 2004 United Kingdom Infantile Spasms Study (UKISS). Ten of 15 (67%) infants with new-onset and previously treated infantile spasms became spasm free within 2 weeks; 4 later recurred. More children with an idiopathic etiology for infantile spasms were spasm free than were symptomatic cases (88% vs 43%, P=0.10). Spasm freedom was equivalent to our most recent 15 infants receiving ACTH, with 13 (87%) responding, P=0.16. Oral prednisolone had fewer adverse effects (53% vs 80%, P=0.10) and was less expensive ($200 vs approximately $70,000) than ACTH. We now routinely recommend oral prednisolone to all families of children with infantile spasms.

The United Kingdom Infantile Spasms Study (UKISS) comparing hormone treatment with vigabatrin on developmental and epilepsy outcomes to age 14 months: a multicentre randomised trial

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. 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. 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). 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.

Infantile Spasms and Epilepsy Currents

The United Kingdom Infantile Spasms Study Comparing Vigabatrin with Prednisolone or Tetracosactide at 14 Days: A Multicentre, Randomised Controlled Trial Lux AL, Edwards SW, Hancock E, Johnson AL, Kennedy CR, Newton RW, O'Callaghan FJ, Verity CM, Osborne JP Lancet 2004;364:1773–1778 Purpose Infantile spasms, 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 multicenter, randomized controlled trial in 150 hospitals in the United Kingdom. The primary outcome was cessation of spasms on days 13 and 14. Minimum doses were vigabatrin, 100 mg/kg/day; oral prednisolone, 40 mg/day; or intramuscular tetracosactide depot, 0.5 mg (40 IU) on alternate days. Analysis was by intention to treat. Results 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 of 30 [70%]; tetracosactide, 19 of 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 receiving hormonal treatments and 28 (54%) of 52 infants receiving vigabatrin. No deaths were recorded. Conclusions Cessation of spasms was more likely in infants given hormonal treatments than in those given vigabatrin. Adverse events were common with both treatments.

The United Kingdom Infantile Spasms Study comparing vigabatrin with prednisolone or tetracosactide at 14 days: a multicentre, randomised controlled trial

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. 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. 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. Cessation of spasms was more likely in infants given hormonal treatments than those given vigabatrin. Adverse events were common with both treatments.