Papers by William Whitehouse
British Paediatric Neurology Association
European Journal of Paediatric Neurology
Archives of Disease in Childhood, 1999
Archives of Disease in Childhood, 2010
Aims To systematically observe the use of four second-line antiepileptic drugs (AEDs) in children... more Aims To systematically observe the use of four second-line antiepileptic drugs (AEDs) in children and the retention, perceived effectiveness, tolerability and safety over 12 months follow-up. Methods All children starting clobazam (CLB), gabapentin (GAB), lamotrigine (LAM) or topiramate (TOP) in a defined period and hospital clinic population were ascertained retrospectively from the hospital pharmacy and paediatric neurology secretaries' databases and clinic letters. A standard data sheet was used to record background data and outcomes at more than 2, 6 and 12 months follow-up. This was a registered clinical audit and service evaluation, and was undertaken as part of medical student's BMedSci courses. Simple statistical analysis was undertaken in SPSS on an intention to treat basis. Results 147 children aged 0.1–17 years have been studied to date: CLB (49), GAB (21), LAM (41), TOP (36), and notes on a further 100 are being interrogated. Epilepsies were evenly split between focal and generalised; apart from GAB (75% on GAB had focal epilepsies). Most were symptomatic or probably symptomatic with a median age of onset 2 years. The AEDs were used after a mean of two other AEDs had been withdrawn (range 1–10). Preliminary analysis showed no major differences in perceived effectiveness between the AEDs, although there was a fall-off of efficacy for all from 2 months to 12 months follow-up: CLB 46–30%, GAB 53–43%, LAM 38–29%, TOP 33–22%. Probably, AED-related adverse events were found in 50% at some stage, although no serious adverse events were recorded. Overall, 54% were still taking the AED after 12 months. Conclusions This is a simple way of auditing the effects of AED treatment in an unselected population with difficult to treat childhood epilepsies and complements data from randomised controlled trials which are usually in more selected populations with shorter follow-up. More data will be available by March 2010, and clinically significant differences in perceived effectiveness might then be confirmed or excluded, and subset analyses undertaken. Comparison with other second-line AEDs levetiracetam, zonisamide, lacosamide and others used in this population will be helpful.
The Lancet Neurology, 2013
Background-Aicardi-Goutières syndrome (AGS) is an inflammatory disorder caused by mutations in an... more Background-Aicardi-Goutières syndrome (AGS) is an inflammatory disorder caused by mutations in any of six genes (TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, and ADAR). The disease is severe and effective treatments are urgently needed. We investigated the status of interferon-related biomarkers in patients with AGS with a view to future use in diagnosis and clinical trials. Methods-In this case-control study, samples were collected prospectively from patients with mutation-proven AGS. The expression of six interferon-stimulated genes (ISGs) was measured by quantitative PCR, and the median fold change, when compared with the median of healthy controls, was used to create an interferon score for each patient. Scores higher than the mean of controls plus two SD (>2•466) were designated as positive. Additionally, we collated historical data for interferon activity, measured with a viral cytopathic assay, in CSF and serum from mutation-positive patients with AGS. We also undertook neutralisation assays of interferon activity in serum, and looked for the presence of autoantibodies against a panel of interferon proteins. Findings-74 (90%) of 82 patients had a positive interferon score (median 12•90, IQR 6•14-20•41) compared with two (7%) of 29 controls (median 0•93, IQR 0•57-1•30). Of the eight patients with a negative interferon score, seven had mutations in RNASEH2B (seven [27%] of all 26 patients with mutations in this gene). Repeat sampling in 16 patients was consistent for the presence or absence of an interferon signature on 39 of 41 occasions. Interferon activity (tested in 147 patients) was negatively correlated with age (CSF, r=−0•604; serum, r=−0•289), and was higher in CSF than in serum in 104 of 136 paired samples. Neutralisation assays suggested that
Intensive Care Medicine, 1996
Human Molecular Genetics, 1994
Recent studies show that patients presenting with cytochrome oxidase (COX) deficiency in infancy ... more Recent studies show that patients presenting with cytochrome oxidase (COX) deficiency in infancy may have reduced mitochondrial DNA (mtDNA) in muscle. The human mitochondrial transcription factor A (h-mtTFA) may be an important regulator of both transcription and replication of mtDNA. h-mtTFA levels were investigated in cell lines which were either free of mtDNA (rho 0) or temporarily depleted by treatment with dideoxycytidine (ddC), and in tissue from three patients with mtDNA depletion and cytochrome oxidase deficiency. h-mtTFA was compared with other mitochondrial proteins such as pyruvate dehydrogenase and porin by Western blotting. The ratio of mtDNA and h-mtTFA mRNA to reference nuclear probes was measured by dual labelling of dot blots. The ratio of mtDNA to nuclear DNA in skeletal muscle was low in muscle in the three patients and in other tissues in one. h-mtTFA was low in cells depleted either permanently or transiently of mtDNA, and this reduction in h-mtTFA roughly paralleled mtDNA levels. Similarly, treatment of rho 0 cell lines with ddC induced a reduction in mtDNA as well as h-mtTFA protein. The relationship between h-mtTFA and mtDNA levels suggests that they may be causally linked. MtDNA depletion was accompanied by an increase in the level of h-mtTFA RNA in the cell lines but low levels in the patient. This suggests that either h-mtTFA regulates mtDNA levels, or that h-mtTFA expression may be regulated by a feedback mechanism initiated by MtDNA Depletion.
European Journal of Paediatric Neurology, 2009
European Journal of Paediatric Neurology, 2009
Posters the infection. Brain MRI scans revealed numerous cortical and subcortical abnormalities s... more Posters the infection. Brain MRI scans revealed numerous cortical and subcortical abnormalities suggested metastasis, but oncological etiology was excluded, as well as boreliosis and other infections. Neurological examination of the patient was normal and oligoclonal streaks were not present in cerebrospinal fluid. EEG recording, VEP, BAEP and SEP evoked potentials were normal too. After 2 months seizures repeated and treatment with sodium valproate was introduced. In brain MRI new numerous hyperintensive focal changes and normal corpus callosum were stated. Spinal cord MRI was normal. Neurological examination was still normal, but the girl suffered from the headaches. The last epileptic tonic clonic seizures occurred after two months. Repeated MRI brain examinations revealed very dynamic increase of the pathological changes, however, still without any abnormalities in neurological examination. The treatment with methylprednisolone was carried out. After 14 months form the onset of the disease, the girl demonstrated left hemiparesis with the left facial nerve paresis, superficial sensibility and swallowing disturbances. The girl has been treated with interferon beta-1a without any side effects and now her estimation in EDSS is 1. Conclusion: In paediatric patients, epilepsy could be the first symptom of MS. P135 A multicentre prospective study of the use of levetiracetam in children in paediatric neurology centres in the Midlands (UK)
European Journal of Paediatric Neurology, 2008
Values of anti-vimentin IgM, IgG antibodies were negative in this group of TSC patients. Could pe... more Values of anti-vimentin IgM, IgG antibodies were negative in this group of TSC patients. Could periodical follow up of NSE and protein S100B plasmatic values be helpful for long-term care for the TSC patients as well as for the children with other neurocutaneous disorders? Supported by IGA MZNR/8889−3, Project VZ0064203,6503. 011NCDP Diagnostic efficiency of anti-vimentin antibodies and neuron-specific enolase in patients with neurofibromatosis von Recklinghausen type 1
European Journal of Paediatric Neurology, 2009
Posters S109 combined disability scores) at different time points will be computed with two-sided... more Posters S109 combined disability scores) at different time points will be computed with two-sided 95% confidence limits. Cox modelling and multivariate logistic regression will be used to explore the relationship between potential prognostic factors, treatment and outcomes. Conclusion: This first international registry for patients with NP-C will provide further, valuable insight into the nature and progression of NP-C over time, and important additional information on patient outcomes from the use of miglustat as a therapy for patients with NP-C.
Child: Care, Health and Development, 2005
Background In the light of recent recommendations regarding the current management of children wi... more Background In the light of recent recommendations regarding the current management of children with possible epilepsy in the UK, different models of care are compared using an existing validated audit tool. Methods The initial clinical assessment process, investigation, management and communication regarding children referred with suspected epilepsy to general paediatric clinics or a paediatric seizure clinic was compared using the British Paediatric Neurology Association (BPNA) audit tool. Results Ninety-three children were included in the comparison. The history and description of the episodes was better documented in the Seizure Clinic (SC). Children's early development (79% vs. 50%) and school performance (86% vs. 42%) were better documented in the SC. Documentation of possible side effects relating to newly prescribed anti-epileptic drugs was poor in both groups (33% vs. 15%). Conclusions Differences between models of epilepsy care can be detected using audit tools although there are some methodological limitations of this particular study. Future similar studies as well as informing local practice can add to the debate on the appropriate way forward in improving the care for children with epilepsy.
BMJ, 1989
figures from Toronto show that at the Ontario Trauma Centre, which has an organised trauma system... more figures from Toronto show that at the Ontario Trauma Centre, which has an organised trauma system, only 6% of patients die with an injury severity score less than their median lethal dose.' The equivalent figure for other roronto hospitals of a similar standard but lacking an organised trauma system was 53%. I also examined the problems entailed in transferring patients with multiple injuries from outlying hospitals to the Royal Infirmary. In this group half were mismanaged in the outlying hospital to an extent that might have contributed to their death. About 350 patients with multiple injuries are admitted each year to the Royal Infirmary, but despite the skill that should accompany this workload up to 70% of the hospital deaths after a road traffic accident seem to be avoidable. The reasons for this are twofold. Firstly, trauma has a low priority within the medical profession to the extent that decision making and treatment are frequently undertaken by junior staff with little experience. Secondly, poor communication exists among the various surgical disciplines, ensuring poor management of patients. The facilities in the hospital for dealing with those with multiple injuries are dreadful. The lack of high dependency and intensive care beds means that patients are usually managed in ordinary wards and if ventilation is required it is usually delayed. The ideal situation is the creation of trauma centres as suggested by the recent report, but until these are established we need to rethink our approach to trauma and to expand existing facilities if my unpalatable statistics for the Royal Infirmary are to be improved.
Archives of Disease in Childhood, 2012
Acta Paediatrica, 2010
Aims: The aim of this study was to develop and refine a decision rule on when to undertake brain... more Aims: The aim of this study was to develop and refine a decision rule on when to undertake brain imaging (BI) in neurologically normal children with headaches.Methods: From the literature and a questionnaire study, a list of red flags (RFs) was drawn‐up. During the prospective 4‐year period, consecutive children with headache were classified according to RFs and the headache diagnosis.Result: Three of 709 (0.4%) neurologically normal children had significant brain abnormalities. BI was carried out in 389 of 498 (78%) children with RFs. Significant abnormalities were found in three of 389 children (0.8%), all had unclassified headache (UH). BI was not arranged for the 211 children with no RFs. None of these developed RFs or abnormal signs on follow‐up for a mean of 13 months.Conclusion: In addition to BI for those with neurological signs, we think BI should be considered for neurologically normal patients with UH and RFs. This would have saved imaging children needlessly: only 10...
Background/objectives: Ataxia Telangiectasia (A-T) is a complex inherited disease that is associa... more Background/objectives: Ataxia Telangiectasia (A-T) is a complex inherited disease that is associated with an increased risk of malignancy. Surveillance guidelines have demonstrated significant health benefits in other cancer predisposition syndromes (CPS). Evidence-based guidelines for cancer screening are not currently used in the UK for people affected by A-T. This study aims to understand how people with A-T and their parents feel about cancer surveillance using whole-body MRI to inform the future development of cancer surveillance guidelines. Design/Methods: We conducted semi-structured interviews of people affected by A-T. Data were analysed inductively using thematic analysis. Results: Nine parents of children with A-T and four adults with A-T were interviewed. Five main themes emerged from the data. All participants viewed cancer screening for children with A-T as invaluable and emphasised the perceived value of early detection. The second theme acknowledged the anxiety assoc...
European Journal of Neurology
The Cerebellum
Ataxia telangiectasia (A-T) is a rare, multisystem progressive condition that typically presents ... more Ataxia telangiectasia (A-T) is a rare, multisystem progressive condition that typically presents in early childhood. In the absence of cure, people with AT require coordinated multidisciplinary care to manage their complex array of needs and to minimize the disease burden. Although symptom management has proven benefits for this population, including improved quality of life and reduced complications, there is a need for guidance specific to the nursing and allied healthcare teams who provide care within the community. A scoping review, adopting the Joanna Briggs Institute methodology, was undertaken. It aimed to identify and map the available expertise from nursing and allied healthcare and management of children and young people with AT ≤ 18 years of age. A rigorous search strategy was employed which generated a total of 21,118 sources of evidence, of which 50 were selected for review following screening by experts. A range of interventions were identified that reported a positive impact on AT related impairments, together with quality of life, indicating that outcomes can be improved for this population. Most notable interventions specific to AT include therapeutic exercise, inspiratory muscle training, and early nutritional assessment and intervention. Further research will be required to determine the full potential of the identified interventions, including translatability to the AT setting for evidence related to other forms of ataxia. Large gaps exist in the nursing and allied health evidence-base, highlighting a need for robust research that includes children and young people with AT and their families to better inform and optimize management strategies.
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Papers by William Whitehouse