Foreword 2

Invited Speakers 3

Oral Presentations 12

Posters 23

Index 59

One hundred and twenty-nine children, 2 to 8 years old, with idiopathic autistic spectrum disorder diagnosed by standard instruments (Childhood Austim Ratings Scale and Autism Diagnostic Observation Schedule) were treated with fluoxetine (0.15 to 0.5mg/kg) for 5 to 76 months (mean 32 to 36 months), with discontinuation trials. Response criteria are described. Family histories were obtained using the family history method in repeated interviews. Fluoxetine response, family history of major affective disorder, and unusual intellectual achievement, pretreatment language, and hyperlexia were used to define a coherent subgroup of autistic spectrum disorder. Statistical analyses were post hoc. Of the children, 22 (17%) had an excellent response, 67 (52%) good, and 40 (31%) fair/poor. Treatment age did not correlate with response. Fluoxetine response correlated robustly with familial major affective disorder and unusual intellectual achievement, and with hyperlexia in the child. Family history of bipolar disorder and of unusual intellectual achievement correlated strongly. Five children developed bipolar disorder during follow-up. Fluoxetine response, family history of major affective disorder (especially bipolar), unusual achievement, and hyperlexia in the children appear to define a homogeneous autistic subgroup. Bipolar disorder, unusual intellectual achievement, and autistic spectrum disorders cluster strongly in families and may share genetic determinants.

Long-term continuous intrathecal baclofen (CITB) infusion is a treatment option used to manage otherwise intractable spasticity and is delivered via an implantable pump. The purpose of this single-center multidisciplinary review was to report on the long-term safety and efficacy of CITB in the treatment of 21 children with intractable severe spasticity of cerebral origin. Nineteen recipients had spastic quadriplegia and two had spastic diplegia. Seven recipients had level IV severity on the Gross Motor Functional Classification System and 14 had level V. Median age at implantation was 12 years (range 4 to 20). Fifteen recipients were male, 6 were female. Seventeen recipients were alive at the end of the follow-up period (31 to 78 months; mean 53, SD 4). The Ashworth scale showed a substantial decrease in spasticity in the upper and lower extremities at 6 months and at the most recent follow-up. The Gross Motor Function Measure and Pediatric Evaluation of Disability Inventory showed no functional change. Most treatment goals were at least partly achieved. Caregivers reported a reduction in use of oral medication for spasticity, and improvements in comfort, function, and ease of care. Caregiver satisfaction was high. During 80 recipient-years of pump operation, 153 treatment-associated adverse events occurred: 27 of these were device-related. There were four deaths unrelated to CITB, including one from acute pancreatitis. Our findings might assist in establishing patient selection criteria and treatment goals, improving patient follow-up, and monitoring adverse events.

This study evaluated the efficacy and safety of three doses of botulinum toxin A (BTX-A; Dysport®) in 125 patients (mean age 5.2 years, SD 2; 54% male)with dynamic equinus spasticity during walking. Participants were randomized to receive Dysport (10, 20, or 30 units/kg) or placebo to the gastrocnemius muscle of both legs. Muscle length was calculated from electrogoniometric measurements and the change in the dynamic component of gastrocnemius shortening at four weeks was prospectively identified as the primary outcome measure. All treatment groups showed statistically significant decreases in dynamic component compared with placebo at 4 weeks. Mean improvement in dynamic component was most pronounced in the 20 units/kg group, being equivalent to an increase in dorsiflexion with the knee extended at 19°, and was still present at 16 weeks. The safety profile of the toxin appears satisfactory.

SPECT can be used to image regional cerebral blood flow (rCBF) and has been shown to help localize the seizure focus in partial epilepsies as part of the presurgical evaluation. Few studies have explored the possible relation between preoperative SPECT and underlying pathology, or any relation to postsurgical outcome. In this study preoperative ictal and interictal rCBF in relation to the histopathological diagnosis and outcome in a series of 35 children (24 females, 11 males; mean age 9.6 years, age range 11 months to 18 years) who had undergone resective surgery for epilepsy were retrospectively evaluated. A correlation between ictal hyperperfusion and the underlying responsible pathology was shown, with a consistent ictal increase in perfusion in developmental pathologies and Rasmussen's encephalitis, and consistent interictal hypoperfusion in hippocampal sclerosis (HS). No rCBF study parameter appeared to relate to outcome but in the group with HS the best outcome was seen in those with localizing ictal rCBF. The varied group of pathologies from hemispherectomy had excellent outcome but the SPECT findings had little to contribute over the abnormalities detected on MRI. In conclusion, rCBF studies remain a useful presurgical investigation in children with partial epilepsy, especially where HS, cortical dysplasia, or inflammatory disease are the underlying pathology. However, rCBF studies add little to the investigation of children with seizures secondary to benign tumours or cerebral infarcts, or where hemispherectomy is the likely preferred surgical option.

Seventy-five families of children with intractable epilepsy but without a severe learning disability (mean age 7 years 1 month, SD 2 years 6 months; range 2 to 12 years) who attended a regional paediatric neurology service, were surveyed. A postal questionnaire was used which included standardized measures of child and family adjustment; forty-eight families responded (64%; 31 males, 17 females). There was no significant difference between responders and non-responders in terms of age, sex, number of other chronic illnesses and disabilities, age at epilepsy diagnosis, seizure type, nor number of antiepileptic drugs currently prescribed (p>0.05). The importance of including multidimensional measures of outcome was highlighted by the finding that epilepsy, pharmacological, and psychosocial factors were differentially associated with specific adjustment difficulties. Two factors appeared to be most pervasively implicated across a range of adjustment problems: frequency of rectal diazepam administration and family patterns of relating to each other (p<0.05). It appeared that duration of seizures (as indicated by frequency of rectal diazepam administration), rather than the frequency of seizures per se, was more pernicious in terms of poor adjustment. Intrafamilial relations (degree of conflict/cohesion and so on) were not only associated with adjustment difficulties in the child, but also with the frequency of seizures themselves. Implications for psychological interventions in intractable epilepsy in childhood are highlighted.

One commonly observed neuroanatomical abnormality in adults with Williams syndrome is an enlarged cerebellum relative to a small cerebrum. Our study is the first to examine neuroanatomy in young children with Williams syndrome. Clinical brain MRI was examined in nine young children with Williams syndrome (mean age 21 months, range 7 to 43 months) relative to nine age- and sex-matched normally developing control children (mean age 29 months, range 20 to 42 months), and two children with undiagnosed developmental disorders (6 and 41 months). Two neuroradiologists who were blinded to participant classification, hypotheses, and regions of interest for the study, sorted the brain scans into two groups on the basis of six neuroanatomical criteria. The raters placed more of the MR scans from children with Williams syndrome into a separate group when they analyzed features of the cerebellum, but not when they analyzed other brain regions. Based on their written comments, the raters focused on the large size of the cerebellum in the children with Williams syndrome. The results lead us to suggest that abnormal cerebellar enlargement is evident in those with Williams syndrome at an early age. Our results are discussed relative to the cognitive delays observed in Williams syndrome versus other disorders such as autism, leading us to suggest that the cerebellum may play a role in cognition.

The objective of this study was to determine the prevalence, circumstances, and outcome of fractures in males with Duchenne muscular dystrophy (DMD) attending neuromuscular clinics. Three hundred and seventy-eight males (median age 12 years, range 1 to 25 years) attending four neuromuscular centres were studied by case-note review supplemented by GP letter or by interview at the time of clinic attendance. Seventy-nine (20.9%) of these patients had experienced fractures. Forty-one percent of fractures were in patients aged 8 to 11 years and 48% in independently ambulant patients. Falling was the most common mechanism of fracture. Upper-limb fractures were most common in males using knee–ankle–foot orthoses (65%) while lower-limb fractures predominated in independently mobile and wheelchair dependent males (54% and 68% respectively). Twenty percent of ambulant males and 27% of those using orthoses lost mobility permanently as a result of the fracture. In a substantial proportion of males, the occurrence of a fracture had a significant impact on subsequent mobility.

This study aimed to investigate the extent to which gesture performance depends on input modality and whether gestural development patterns differ in children with and without developmental coordination disorder (DCD). Therefore, development of limb gesture was studied in 140 children – 105 control children(94 males, 11 females) and in 35 children with DCD (29 males, six females) divided into three age bands: 5 to 6 years, 7 to 8 years, and 9 to 10 years. Transitive gestural skills were investigated through four input modalities: Imitation, Visual plus Tactile , Visual, and Verbal. Results indicate that limb gestural skills in normally developing children follow a progressive maturation pattern: Imitation, Visual plus Tactile, and visual routes appear to mature before the verbal route and appear to be available earlier to enable the child to perform a correct gesture. The performance of children with DCD throughout the four modalities suggested a general maturational delay. When gestures were required through the Verbal modality, there was a specific deficit in using sensory–motor information and in integrating it into a motor representation. In the Verbal modality, children with DCD performed consistently worse than their control peers and the difference in performance tended to increase rather than improve with age.

This report describes the case history of two male siblings with sensorineural hearing loss and an enlarged vestibular aqueduct (EVA). Sibling 1 presented with a history of intermittent self-limiting ataxia and hearing loss at the age of 25 months and sibling 2 presented with a similar history at the age of 18 months. MRI showed an enlarged endolymphatic duct and sac bilaterally in both children. Perchlorate discharge tests were positive in both infants leading to a diagnosis of Pendred syndrome. A number of conditions associated with EVA are discussed with a view to devising management strategies.

Non-ketotic hyperglycinemia (NKH), also termed glycine encephalopathy (MIM 605899), is an autosomal recessive inborn error of glycine degradation which leads to severe neurological symptoms and profound psychomotor disability. In NKH, glycine accumulates in all body fluids and tissues, including the CNS. The biochemical hallmark of NKH is increased glycine concentration in the plasma and to an even greater extent in the CSF, leading to an elevation of the CSF:plasma glycine ratio (C:PGR) to above 0.08 (normal <0.04). The fundamental defect is in the glycine cleavage system (GCS), a multienzyme complex located in the inner mitochondrial membrane of the liver, kidney, brain, and placenta. It consists of four individual protein components termed P (a pyridoxal phosphate-dependent glycine decarboxylase), H (a lipoic acid-containing hydrogen carrier protein), T (a tetrahydrofolate-dependent protein), and L (a lipoamide dehydrogenase). In more than 80% of patients the defect is in the P protein (MIM 238300), but defects in the T (MIM 238310) and H (MIM 238330) proteins have also been described. The pathogenesis of NKH is related to the properties of glycine as an excitatory neurotransmitter acting via the N-methyl-D-aspartate receptor in the cortex and an inhibitory neurotransmitter in the brainstem and spinal cord.