Prednisolone or tetracosactide depot for infantile epileptic spasms syndrome? A prospective analysis of data embedded within two randomised controlled trials.

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 outcome of surgical management of subependymal giant cell astrocytoma in tuberous sclerosis complex.

Objectives: The indications for surgery and outcomes of patients who underwent surgical removal of subependymal giant cell astrocytomas (SEGAs) in our institution between 2000 and 2011 were reviewed.

Methods: We reviewed the clinical details of 16 patients with a diagnosis of Tuberous Sclerosis Complex (TSC) who underwent surgery for SEGA in Bristol since 2000. We collected information on age, sex, epilepsy history and cognitive status.

Phospholipase C beta 1 deficiency is associated with early-onset epileptic encephalopathy.

The epileptic encephalopathies of infancy and childhood are a collection of epilepsy disorders characterized by refractory, severe seizures and poor neurological outcome, in which the mechanism of disease is poorly understood. We report the clinical presentation and evolution of epileptic encephalopathy in a patient, associated with a loss-of-function mutation in the phospholipase C-β 1 gene. We ascertained a consanguineous family containing a male infant who presented with early-onset epileptic encephalopathy for detailed clinical phenotyping and molecular genetic investigation.

Dancing Eye Syndrome associated with spontaneous recovery and normal neurodevelopment.

Five patients with spontaneously recovering Dancing Eye Syndrome/Opsoclonus Myoclonus Syndrome are described. Age at presentation ranged from 4 to 19 months. Four had symptoms of fever and a coryzal illness within days to a few weeks prior to the onset.

Treatment of infantile spasms.

Background: Infantile spasms (West's Syndrome) is a syndrome which includes a peculiar type of epileptic seizure, the spasms, and an electroencephalogram (EEG) abnormality often called hypsarrhythmia. Psychomotor retardation is frequently found at follow up. Approximately two thirds of affected infants will have a detectable underlying neurological abnormality, but still little is known about the pathophysiological basis for infantile spasms and treatment remains problematic.

The influence of etiology upon ictal semiology, treatment decisions and long-term outcomes in infantile spasms and West syndrome.

Studying infantile spasms is challenging because there are so many aspects of variation that introduce potential bias. These might relate to the many underlying etiologies, and variations in clinical semiology and electroencephalographic features that relate more to age or timing of investigation than to the underlying epilepsy or seizures type. New gene defects associated with the CDKL5/STK9 and ARX genes are associated with infantile spasms, but these illustrate that, when studying neurodevelopmental outcomes, it is necessary to deal also with heterogeneity at the level of genotype-phenotype correlation.

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.

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.

Effect of melatonin dosage on sleep disorder in tuberous sclerosis complex.

We report a randomized, double-blind, controlled, crossover trial investigating the response to oral melatonin using two dose regimens in patients with sleep disorders associated with tuberous sclerosis complex. Eight outpatients with tuberous sclerosis complex and sleep disorder received either 5 or 10 mg of melatonin. Sleep latency, total sleep time, number of awakenings, and seizure frequency were recorded in sleep and seizure diaries.

Melatonin excretion in normal children and in tuberous sclerosis complex with sleep disorder responsive to melatonin.

To determine normal melatonin excretion patterns in healthy children without sleep disorder and to compare these with those of patients with tuberous sclerosis complex and sleep disorder responsive to exogenous melatonin, we measured 6-sulfatoxymelatonin excretion in 21 healthy children and in 7 patients with tuberous sclerosis complex and sleep disorder responsive to melatonin (a 5 mg oral dose increasing total sleep time). Total excretion, cosinor percentage, and acrophase time of 6-sulfatoxymelatonin excretion were estimated. In normal children, total 6-sulfatoxymelatonin excretion was range 11.

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

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.

A proposal for case definitions and outcome measures in studies of infantile spasms and West syndrome: consensus statement of the West Delphi group.

Purpose: To reach a broad consensus on case definitions, outcomes, and outcome measures that will ease future study design and facilitate comparison of data from different studies of infantile spasms and West syndrome.

Methods: Persons who had recently presented or published first-author original research in this field were invited to participate in an e-mail Delphi process and to invite other investigators or clinicians who they thought might participate.

Results: The process consisted of six rounds, anonymous except to the facilitator.

An epidemiological study of renal pathology in tuberous sclerosis complex.

Objectives: To report the frequency of renal symptoms and complications of patients with tuberous sclerosis complex (TSC), to describe the ultrasonographic appearance of the kidneys in a population-based sample, and to investigate the relationship between a history of renal haemorrhage and renal lesions identified by ultrasonography.

Patients And Methods: As part of an epidemiological study, 179 patients with TSC were identified as living in the Wessex Region in the South of England. Patients were interviewed and examined in their homes, to elicit the presence of renal symptoms or a history of renal complications.

Nonsense-mediated RNA decay in the TSC1 gene suggests a useful tool pre- and post-positional cloning.

Many mRNAs carrying mutations that are predicted to encode a truncated protein are subject to a mechanism known as nonsense-mediated mRNA decay (NMD), which results in reduced levels of mutant transcript. Tuberous sclerosis (TSC), an autosomal dominant neurocutaneous disorder with mutations in either of two genes, TSC1 or TSC2, requires comprehensive screening of both genes for molecular diagnosis. Virtually all TSC1 mutations are predicted to truncate the protein product.