Morag Andrew

Deep brain stimulation in childhood: an effective treatment for early onset idiopathic generalised dystonia

Background: Early onset idiopathic generalised dystonia is a progressive and profoundly disabling condition. Medical treatment may ameliorate symptoms. However, many children have profound, intractable disability including the loss of ambulation and speech, and difficulties with feeding. Following the failure of medical management, deep brain stimulation (DBS) of the globus pallidus internus (GPi) has emerged as an alternative treatment for the disorder. Methods: We describe four children who presented with dystonia. Results: Following the failure of a range of medical therapies, DBS systems were implanted in the GPi in an attempt to ameliorate the children’s disabilities. All children found dystonic movements to be less disabling following surgery. Compared with preoperative Burke, Fahn and Marsden Dystonia Rating Scale scores, postoperative scores at 6 months were improved. Conclusions: DBS is effective in improving symptoms and function in children with idiopathic dystonia refractory to medical treatment. Whilst surgery is complex and can be associated with intraoperative and postoperative complications, this intervention should be considered following the failure of medical therapy.

How common is childhood myasthenia? The UK incidence and prevalence of autoimmune and congenital myasthenia

Objective To ascertain the frequency of childhood myasthenia in the UK. Specifically, we aimed to identify the detected incidence of autoimmune myasthenia and the detected prevalence of genetically confirmed congenital myasthenic syndrome (CMS) in children. Methods All children under 18 years of age on 31 December 2009 with a confirmed CMS genetic mutation were identified by the only UK laboratory undertaking CMS genetic testing. All cases with positive acetylcholine receptor (AChR) and muscle specific kinase (MuSK) receptor antibodies in the 5 years between 2003 and 2007 inclusive were identified by the testing laboratories. UK census data from 2001 were used as the denominator for analyses. Results The UK detected prevalence of genetically confirmed CMS was 9.2 per million children under 18 years of age. CMS was equally prevalent in girls and boys. CHRNE, RAPSN and DOK7 were the most commonly identified mutations. Prevalence varied across geographical regions in England (between 2.8 and 14.8 per million children). The mean incidence of antibody-positive autoimmune myasthenia was 1.5 per million children per year over the period of the study. Girls were affected more frequently than boys; this difference persisted across the age range. Antibodies were identified during the neonatal period in 17 children. Conclusions This laboratory based study shows that childhood myasthenia is very rare. This condition is treatable, and these definitive detected incidence and prevalence data can be used to help plan diagnostic and supporting services for affected children and their families, and maximise research opportunities.

Growth in Cerebral Palsy

Cerebral palsy is often accompanied by abnormalities of growth and nutrition; children with severe motor impairments are most at risk. Nutrition, neurological, and endocrine factors all contribute to suboptimal growth. Poor growth and nutrition are associated with poor general health outcomes and reduced levels of participation, and therefore warrant careful evaluation and appropriate intervention. The lack of normative data combined with the complex interaction of nutrition and nonnutrition factors contributing to growth in this population present real difficulties in management. Particular care is needed to avoid overfeeding and the resultant increase in fat mass and associated morbidity.

Optimising nutrition to improve growth and reduce neurodisabilities in neonates at risk of neurological impairment, and children with suspected or confirmed cerebral palsy

BackgroundNeurological impairment is a common sequelae of perinatal brain injury. Plasticity of the developing brain is due to a rich substrate of developing neurones, synaptic elements and extracellular matrix. Interventions supporting this inherent capacity for plasticity may improve the developmental outcome of infants following brain injury. Nutritional supplementation with combination docosahexaenoic acid, uridine and choline has been shown to increase synaptic elements, dendritic density and neurotransmitter release in rodents, improving performance on cognitive tests. It remains elusive whether such specific ‘neurotrophic’ supplementation enhances brain plasticity and repair after perinatal brain injury.Methods/DesignThis is a two year double-blind, randomised placebo controlled study with two cohorts to investigate whether nutritional intervention with a neurotrophic dietary supplement improves growth and neurodevelopmental outcomes in neonates at significant risk of neurological impairment (the D1 cohort), and infants with suspected or confirmed cerebral palsy (the D2 cohort).120 children will be randomised to receive dietetic and nutritional intervention, and either active supplement or placebo. Eligible D1 neonates are those born <30+6 weeks gestation with weight <9th centile, ≤30+6 weeks gestation and Grade II, III or IV Intra-Ventricular Haemorrhage or periventricular white matter injury, or those born at 31-40+28 weeks gestation, with Sarnat grade I or II or III Hypoxic Ischaemic Encephalopathy or neuroimaging changes compatible with perinatal brain injury. Eligible D2 infants are those aged 1-18 months with a suspected or confirmed clinical diagnosis of cerebral palsy. The primary outcome measure is composite cognitive score on the Bayley Scales of Infant and Toddler Development III at 24 months. Secondary outcomes include visuobehavioural and visual neurophysiological assessments, and growth parameters including weight, height, and head circumference.DiscussionThis is the first study to supplement neonates and infants with perinatal brain injury with the combination of factors required for healthy brain development, throughout the period of maximal brain growth. A further study strength is the comprehensive range of outcome measures employed. If beneficial, supplementation with brain phosphatide precursors could improve the quality of life of thousands of children with perinatal brain injury.Trial registrationCurrent Controlled trials: ISRCTN39264076 (registration assigned 09/11/2012), ISRCTN15239951 (registration assigned 23/04/2010).

Deep brain stimulation in childhood: An effective treatment for early onset generalised idiopathic dystonia

Background: Early onset idiopathic generalised dystonia is a progressive and profoundly disabling condition. Medical treatment may ameliorate symptoms. However, many children have profound, intractable disability including the loss of ambulation and speech, and difficulties with feeding. Following the failure of medical management, deep brain stimulation (DBS) of the globus pallidus internus (GPi) has emerged as an alternative treatment for the disorder. Methods: We describe four children who presented with dystonia. Results: Following the failure of a range of medical therapies, DBS systems were implanted in the GPi in an attempt to ameliorate the children’s disabilities. All children found dystonic movements to be less disabling following surgery. Compared with preoperative Burke, Fahn and Marsden Dystonia Rating Scale scores, postoperative scores at 6 months were improved. Conclusions: DBS is effective in improving symptoms and function in children with idiopathic dystonia refractory to medical treatment. Whilst surgery is complex and can be associated with intraoperative and postoperative complications, this intervention should be considered following the failure of medical therapy.

Nutritional intervention and neurodevelopmental outcome in infants with suspected cerebral palsy: the Dolphin infant double-blind randomized controlled trial

To investigate whether docosahexaenoic acid (DHA), choline, and uridine‐5‐monophosphate (UMP) supplementation improves neurodevelopmental outcome in infants with suspected cerebral palsy (CP) versus a comparison group of children.

Nutritional intervention and neurodevelopmental outcome in newborn infants at risk of neurodevelopmental impairment: the Dolphin neonatal double-blind randomized controlled trial.

To investigate whether neonates at risk for neurodevelopmental impairment have improved neurodevelopment after docosahexaenoic acid, choline, and uridine‐5‐monophosphate supplementation versus controls.

Gastrointestinal Problems in Children with Cerebral Palsy

Feeding and gastrointestinal difficulties are common in children with cerebral palsy and if not appropriately managed can result in undernutrition, poor growth and worsened general health. Gastrointestinal difficulties include oropharyngeal dysfunction, drooling, foregut dysmotility and gastro-oesophageal reflux as a result of gastro-oesophageal dysmotility, retching, delayed gastric emptying and chronic constipation. The assessment and management of children with cerebral palsy and comorbid gastrointestinal problems are best performed within a multidisciplinary team experienced in the management of children with CP and gastrointestinal problems. This chapter considers the gastrointestinal problems experienced by children with cerebral palsy and outlines current management strategies.