The early course and treatment of posttraumatic stress disorder in very young children: diagnostic prevalence and predictors in hospital-attending children and a randomized controlled proof-of-concept trial of trauma-focused cognitive therapy, for 3- to 8-year-olds.

BACKGROUND: The introduction of developmentally adapted criteria for posttraumatic stress disorder (PTSD) has improved the identification of ≤6-year-old children with clinical needs. Across two studies, we assess predictors of the development of PTSD in young children (PTSD-YC), including the adult-led acute stress disorder (ASD) diagnosis, and provide proof of principle for cognitive-focused therapy for this age range, with the aim of increasing treatment options for children diagnosed with PTSD-YC. METHOD: Study 1 (N = 105) assessed ASD and PTSD-YC diagnosis in 3- to 8-year-old children within one month and at around three months following attendance at an emergency room. Study 2 (N = 37) was a preregistered (www.isrctn.com/ISRCTN35018680) randomized controlled early-phase trial comparing CBT-3M, a cognitive-focused intervention, to treatment-as-usual (TAU) delivered within the UK NHS to 3- to 8-year-olds diagnosed with PTSD-YC. RESULTS: In Study 1, the ASD diagnosis failed to identify any young children. In contrast, prevalence of acute PTSD-YC (minus the duration requirement) was 8.6% in the first month post-trauma and 10.1% at 3 months. Length of hospital stay, but no other demographic or trauma-related characteristics, predicted development of later PTSD-YC. Early (within one month) diagnosis of acute PTSD-YC had a positive predictive value of 50% for later PTSD-YC. In Study 2, most children lost their PTSD-YC diagnosis following completion of CBT-3M (84.6%) relative to TAU (6.7%) and CBT-3M was acceptable to recipient families. Effect sizes were also in favor of CBT-3M for secondary outcome measures. CONCLUSIONS: The ASD diagnosis is not fit for purpose in this age-group. There was a strong and encouraging signal of putative efficacy for young children treated using a cognitive-focused treatment for PTSD, and a larger trial of CBT-3M is now warranted.

Advancing methodology for scoping reviews: recommendations arising from a scoping literature review (SLR) to inform transformation of Children and Adolescent Mental Health Services.

BACKGROUND: There is consensus that health services commissioning and clinical practice should be driven by scientific evidence. However, workload pressures, accessibility of peer reviewed publications and skills to find, appraise, and synthesise relevant evidence are often cited as barriers to uptake of research evidence by practitioners and commissioners alike. In recent years a growing requirement for rapid evidence synthesis to inform commissioning decisions about healthcare service delivery and provision of care contributed to an increasing popularity of scoping literature reviews (SLRs). Yet, comprehensive guidelines for conducting and reporting SLRs are still relatively scarce. METHODS: The exemplar review used as a worked example aimed to provide a readily available, comprehensive, and user-friendly repository of research evidence for local commissioners to help them make evidence-informed decisions about redesigning East of England Children and Adolescent Mental Health Services. In conducting the review, we were broadly guided by Arksey and O'Malley's framework, however some modifications were made at different stages to better reflect the largely pragmatic objective of this review. This paper compares the methodology used with existing methodological frameworks for scoping studies, to add to the existing knowledge base. RESULTS: We proposed the following advancements to the existing SLR frameworks: (i) Assemble a research team with complementary skills and expertise; (ii); Draw on expertise of external partners, particularly practitioners, decision-makers and commissioners who will be translating findings into practice; (iii) Pre-register the review protocol. Keep a detailed record of all steps and decisions and consider how they would impact on generalisability and utility of review findings; (iv) Use systematic procedures for literature searchers, selection of studies, data extraction and analysis; (v) If feasible, appraise the quality of included evidence; (vi) Be transparent about limitations of findings. CONCLUSIONS: Despite some methodological limitations, scoping literature reviews are a useful method of rapidly synthesising a large body of evidence to inform commissioning and transformation of CAMHS. SLRs allow researchers to start with a broader questions, to explore the issue from different perspectives and perhaps find more comprehensive solutions that are not only effective, but also accounted for their feasibility and acceptability to key stakeholders.

Feasibility of School-Based Identification of Children and Adolescents Experiencing, or At-risk of Developing, Mental Health Difficulties: a Systematic Review.

Under-identification of mental health difficulties (MHD) in children and young people contributes to the significant unmet need for mental health care. School-based programmes have the potential to improve identification rates. This systematic review aimed to determine the feasibility of various models of school-based identification of MHD. We conducted systematic searches in Medline, Embase, PsycINFO, ERIC, British Education Index, and ASSIA using terms for mental health combined with terms for school-based identification. We included studies that assessed feasibility of school-based identification of students in formal education aged 3-18 with MHD, symptomatology of MHD, or exposed to risks for MHD. Feasibility was defined in terms of (1) intervention fit, (2) cost and resource implications, (3) intervention complexity, flexibility, manualisation, and time concerns, and (4) adverse events. Thirty-three studies met inclusion criteria. The majority focused on behavioural and socioemotional problems or suicide risk, examined universal screening models, and used cross-sectional designs. In general, school-based programmes for identifying MHD aligned with schools' priorities, but their appropriateness for students varied by condition. Time, resource, and cost concerns were the most common barriers to feasibility across models and conditions. The evidence base regarding feasibility is limited, and study heterogeneity prohibits definitive conclusions about the feasibility of different identification models. Education, health, and government agencies must determine how to allocate available resources to make the widespread adoption of school-based identification programmes more feasible. Furthermore, the definition and measurement of feasibility must be standardised to promote any future comparison between models and conditions.

A systematic review of effectiveness and cost-effectiveness of school-based identification of children and young people at risk of, or currently experiencing mental health difficulties.

BACKGROUND: Although school-based programmes for the identification of children and young people (CYP) with mental health difficulties (MHD) have the potential to improve short- and long-term outcomes across a range of mental disorders, the evidence-base on the effectiveness of these programmes is underdeveloped. In this systematic review, we sought to identify and synthesise evidence on the effectiveness and cost-effectiveness of school-based methods to identify students experiencing MHD, as measured by accurate identification, referral rates, and service uptake. METHOD: Electronic bibliographic databases: MEDLINE, Embase, PsycINFO, ERIC, British Education Index and ASSIA were searched. Comparative studies were included if they assessed the effectiveness or cost-effectiveness of strategies to identify students in formal education aged 3-18 years with MHD, presenting symptoms of mental ill health, or exposed to psychosocial risks that increase the likelihood of developing a MHD. RESULTS: We identified 27 studies describing 44 unique identification programmes. Only one study was a randomised controlled trial. Most studies evaluated the utility of universal screening programmes; where comparison of identification rates was made, the comparator test varied across studies. The heterogeneity of studies, the absence of randomised studies and poor outcome reporting make for a weak evidence-base that only generate tentative conclusions about the effectiveness of school-based identification programmes. CONCLUSIONS: Well-designed pragmatic trials that include the evaluation of cost-effectiveness and detailed process evaluations are necessary to establish the accuracy of different identification models, as well as their effectiveness in connecting students to appropriate support in real-world settings.

Acceptability of screening for mental health difficulties in primary schools: a survey of UK parents.

BACKGROUND: Many children and young people experiencing mental health difficulties (MHD) do not access care, often due to inadequate identification. Schools have a unique potential to improve early identification; however, evidence is limited regarding the acceptability of school-based identification programmes. This study aimed to examine parents' beliefs about the acceptability of school-wide MHD screening in primary schools. METHODS: We collaborated with experts in school-based mental health to develop a questionnaire to measure parental attitudes toward school-wide MHD screening. The questionnaire contained 13 items relating to acceptability; three open-text boxes for comments on harms, benefits, and screening in general; and four questions that captured demographic information. Parents of children attending four primary schools in Cambridgeshire and Norfolk completed the questionnaire. We calculated counts, percentages, and means for each statement, and analysed responses to open-ended questions using content analysis. RESULTS: Two hundred ninety parents returned the questionnaire across the four schools (61% response rate). In the 260 questionnaires analysed, a total of 254 parents (98%) believed that it is important to identify MHD early in life, and 251 (97%) believed that schools have an important role in promoting pupils' emotional health. The majority of parents (N = 213; 82%) thought that screening would be helpful, although 34 parents (13%) thought that screening would be harmful. Perceived harms of screening included inaccurate identification, stigmatisation, and low availability of follow-up care. There was no clear consensus regarding how to obtain consent or provide feedback of screening results. There were no significant differences in responses according to ethnicity, gender, age, or school. CONCLUSIONS: Results suggest that most parents within the socio-demographic context of our study will accept MHD screening within primary schools, and that school-based screening is viable from the perspective of parents. The comments provided about potential harms as well as suggestions for programme delivery are relevant to inform the development and evaluation of acceptable and sustainable school-based identification models. Implementation and scale-up of such programmes will require further understanding of the perspectives of mental health professionals, school staff, and the general public as well as further evaluation against the established standards for identification programmes.

Intellectual development before and after the onset of infantile spasms: a controlled prospective longitudinal study in tuberous sclerosis.

OBJECTIVE: Infantile spasms (IS) have long been suspected to be a risk factor for impairment in intellectual development, but there are no controlled, prospective longitudinal data in well-characterized conditions to confirm this suspicion. We tested the hypothesis in a longitudinal study of children with tuberous sclerosis (TS), who have a high risk of developing IS. METHODS: Eleven infants with TS were recruited and studied longitudinally using the Mullen Scales of Early Learning. Seizure histories were assessed using a structured parent interview and by review of medical notes. Intellectual development was examined in relation to the onset and length of exposure to IS and other types of seizures. RESULTS: Six children developed IS and five children developed other types of seizure disorders. Among those that developed IS, estimated mean IQ dropped significantly (nonparametric test for trend p = 0.002) from 92 (prior to onset of spasms) to 73 (after exposure to IS for a month or less) and 62 (after exposure to IS for more than a month). By contrast, there was no significant drop in estimated IQ among the five infants exposed to other types of seizure disorders (nonparametric test for trend p = 0.9). All six children exposed to infantile spasms developed clinically significant intellectual impairment. SIGNIFICANCE: These data provide the first clear evidence of clinically significant, dose dependent, impairment in intellectual development following exposure to infantile spasms. The mechanisms underlying this developmental impairment and methods for preventing it require in depth study.

Leveraging Administrative Data to Better Understand and Address Child Maltreatment: A Scoping Review of Data Linkage Studies.

BACKGROUND: This scoping review aimed to overview studies that used administrative data linkage in the context of child maltreatment to improve our understanding of the value that data linkage may confer for policy, practice, and research. METHODS: We searched MEDLINE, Embase, PsycINFO, CINAHL, and ERIC electronic databases in June 2019 and May 2020 for studies that linked two or more datasets (at least one of which was administrative in nature) to study child maltreatment. We report findings with numerical and narrative summary. RESULTS: We included 121 studies, mainly from the United States or Australia and published in the past decade. Data came primarily from social services and health sectors, and linkage processes and data quality were often not described in sufficient detail to align with current reporting guidelines. Most studies were descriptive in nature and research questions addressed fell under eight themes: descriptive epidemiology, risk factors, outcomes, intergenerational transmission, predictive modelling, intervention/service evaluation, multi-sector involvement, and methodological considerations/advancements. CONCLUSIONS: Included studies demonstrated the wide variety of ways in which data linkage can contribute to the public health response to child maltreatment. However, how research using linked data can be translated into effective service development and monitoring, or targeting of interventions, is underexplored in terms of privacy protection, ethics and governance, data quality, and evidence of effectiveness.

Determining stakeholder priorities and core components for school-based identification of mental health difficulties: A Delphi study.

Only approximately half of children and young people (CYP) with mental health difficulties access mental health services in England, with under-identification of need as a contributing factor. Schools may be an ideal setting for identifying mental health difficulties in CYP, but uncertainty remains about the processes by which these needs can best be identified and addressed. In this study, we conducted a two-round, three-panel Delphi study with parents, school staff, mental health practitioners, and researchers to inform the development of a program to identify mental health difficulties in primary schools. We aimed to assess and build consensus regarding (a) the aims of such a program, (b) identification model preferences, (c) key features of the identification model, and (d) key features of the implementation model. A total of 54 and 42 participants completed the Round 1 and 2 questionnaires, respectively. In general, responses indicated that all three panels supported the idea of school-based identification of mental health difficulties. Overall, 53 of a possible 99 items met the criteria for inclusion as program core components. Five main priorities emerged, including that (a) the program should identify children experiencing mental health difficulties across the continuum of severity, as well as children exposed to adversity, who are at greater risk of mental health difficulties; (b) the program should train staff and educate pupils about mental health in parallel; (c) parental consent should be obtained on an opt-out basis; (d) the program must include clear mechanisms for connecting identified pupils to care and support; and (e) to maximize implementation success, the program needs to lie within a school culture that values mental health and wellbeing. In highlighting these priorities, our study provides needed stakeholder consensus to guide further development and evaluation of mental health interventions within schools.

DECRYPT trial: study protocol for a phase II randomised controlled trial of cognitive therapy for post-traumatic stress disorder (PTSD) in youth exposed to multiple traumatic stressors.

BACKGROUND: Post-traumatic stress disorder (PTSD) is a distressing and disabling condition that affects significant numbers of children and adolescents. Youth exposed to multiple traumas (eg, abuse, domestic violence) are at particular risk of developing PTSD. Cognitive therapy for PTSD (CT-PTSD), derived from adult work, is a theoretically informed, disorder-specific form of trauma-focused cognitive-behavioural therapy. While efficacious for child and adolescent single-event trauma samples, its effectiveness in routine settings with more complex, multiple trauma-exposed youth has not been established. The Delivery of Cognitive Therapy for Young People after Trauma randomised controlled trial (RCT) examines the effectiveness of CT-PTSD for treating PTSD following multiple trauma exposure in children and young people in comparison with treatment as usual (TAU). METHODS/DESIGN: This protocol describes a two-arm, patient-level, single blind, superiority RCT comparing CT-PTSD (n=60) with TAU (n=60) in children and young people aged 8-17 years with a diagnosis of PTSD following multiple trauma exposure. The primary outcome is PTSD severity assessed using the Children's Revised Impact of Event Scale (8-item version) at post-treatment (ie, approximately 5 months post-randomisation). Secondary outcomes include structured interview assessment for PTSD, complex PTSD symptoms, depression and anxiety, overall functioning and parent-rated mental health. Mid-treatment and 11-month and 29-month post-randomisation assessments will also be completed. Process-outcome evaluation will consider which mechanisms underpin or moderate recovery. Qualitative interviews with the young people, their families and their therapists will be undertaken. Cost-effectiveness of CT-PTSD relative to TAU will be also be assessed. ETHICS AND DISSEMINATION: This trial protocol has been approved by a UK Health Research Authority Research Ethics Committee (East of England-Cambridge South, 16/EE/0233). Findings will be disseminated broadly via peer-reviewed empirical journal articles, conference presentations and clinical workshops. TRIAL REGISTRATION: ISRCTN12077707. Registered 24 October 2016 (http://www.isrctn.com/ISRCTN12077707). Trial recruitment commenced on 1 February 2017. It is anticipated that recruitment will continue until June 2021, with 11-month assessments being concluded in May 2022.

Evaluating the CYP-IAPT transformation of child and adolescent mental health services in Cambridgeshire, UK: a qualitative implementation study.

BACKGROUND: The Children and Young People's Improving Access to Psychological Therapies (CYP-IAPT) programme was introduced to transform Child and Adolescent Mental Health Services (CAMHS) across England. The programme comprised a set of principles that local CAMHS partnerships were expected to operationalise and embed with the aim of increasing access to services and improving the quality of care. This study explored how the implementation of the CYP-IAPT programme was executed and experienced by CAMHS professionals in the county of Cambridgeshire (UK), and the extent to which the CYP-IAPT principles were perceived to be successfully embedded into everyday practice. METHODS: We analysed 275 documents relating to the CYP-IAPT programme issued between 2011 and 2015. We also conducted a thematic analysis of 20 qualitative interviews, undertaken at two time points, with professionals from three CAMHS teams in Cambridgeshire. Analysis was informed by implementation science frameworks. RESULTS: Document analysis suggested that the CYP-IAPT programme was initially not clearly defined and lacked guidance on how to operationalise key programme principles and apply them in everyday practice. There was also a degree of programme evolution over time, which made it difficult for local stakeholders to understand the scope and aims of CYP-IAPT. Interviews with staff showed low coherent understanding of the programme, variable levels of investment among stakeholders and difficulties in collaborative working. Barriers and facilitators to programme implementation were identified at individual, service and strategic levels. These in turn impacted the local implementation efforts and sustainability of the programme in Cambridgeshire. CONCLUSIONS: We identified factors relating to programme design and national and local implementation planning, as well as features of inner and outer context, which impacted on the delivery and sustainability of the programme. These findings can be drawn upon to inform the development and delivery of other local and national quality improvement (QI) initiatives relating to children and young people's mental health.

Brief Report: An Evaluation of the Social Communication Questionnaire as a Screening Tool for Autism Spectrum Disorder in Young People Referred to Child & Adolescent Mental Health Services.

The SCQ is a widely used screening measure for the assessment of autism spectrum disorder (ASD). However, its sensitivity and specificity when used with older children in the context of community Child & Adolescent Mental Health services is unclear. Seventy-seven (Mean age = 12.8 years) young people with suspected ASD were screened using parent- and teacher-reported SCQ's before completing a comprehensive diagnostic assessment. Of the 77 young people included, 44 (57%) met criteria for an ASD diagnosis. Our results indicated that regardless of informant, SCQ scores did not significantly predict the outcome of the diagnostic assessment. Based on the published cut-off score for the SCQ, Receiver Operating Characteristic curve analyses revealed a lower than expected sensitivity and specificity. This suggests that the SCQ is not an effective screening tool when used in the context of community Child & Adolescent Mental Health services.

Delphi study to identify key features of community-based child and adolescent mental health services in the East of England.

OBJECTIVE: To identify priorities for the delivery of community-based Child and Adolescent Mental health Services (CAMHS). DESIGN: (1) Qualitative methods to gather public and professional opinions regarding the key principles and components of effective service delivery. (2) Two-round, two-panel adapted Delphi study. The Delphi method was adapted so professionals received additional feedback about the public panel scores. Descriptive statistics were computed. Items rated 8-10 on a scale of importance by ≥80% of both panels were identified as shared priorities. SETTING: Eastern region of England. PARTICIPANTS: (1) 53 members of the public; 95 professionals from the children's workforce. (2) Two panels. Public panel: round 1,n=23; round 2,n=16. Professional panel: round 1,n=44; round 2,n=33. RESULTS: 51 items met the criterion for between group consensus. Thematic grouping of these items revealed three key findings: the perceived importance of schools in mental health promotion and prevention of mental illness; an emphasis on how specialist mental health services are delivered rather than what is delivered (ie, specific treatments/programmes), and the need to monitor and evaluate service impact against shared outcomes that reflect well-being and function, in addition to the mere absence of mental health symptoms or disorders. CONCLUSIONS: Areas of consensus represent shared priorities for service provision in the East of England. These findings help to operationalise high level plans for service transformation in line with the goals and needs of those using and working in the local system and may be particularly useful for identifying gaps in ongoing transformation efforts. More broadly, the method used here offers a blueprint that could be replicated by other areas to support the ongoing transformation of CAMHS.

The Early Childhood Epilepsy Severity Scale (E-Chess).

PURPOSE: We have developed the Early Childhood Epilepsy Severity Scale (E-Chess) to quantify the severity of epilepsy in infants and young children with tuberous sclerosis as an aid to the evaluation of treatment efficacy and the investigation of the influence of epilepsy severity on development. METHODS: Twenty infants aged 11-36 months with a diagnosis of tuberous sclerosis participated in the study. From the literature, six potential measures of epilepsy severity were identified: time period over which seizures occurred; seizure frequency; number of seizure types; occurrence and duration of status epilepticus; number of anticonvulsant medications used; response to treatment. The variables were given a score, usually from 0 to 3, a higher score indicating greater severity. For each child, these variables were scored over consecutive 1 year time periods by three independent raters. We employed restricted and nonrestricted factor analytic models to identify the latent structure of the six items. RESULTS: The six severity items had a unidimensional structure. All severity indicators loaded highly on the latent epilepsy severity factor (>0.77), with the exception of the status indicator which had a poor loading (<0.40) and was excluded from further analyses. Goodness of fit indices were all well within the acceptable criteria for model fit. The E-Chess score at 12 months was significantly predictive of scores at 24 and 36 months. CONCLUSIONS: A single continuous latent variable accounts for the variation in five of the six epilepsy severity indicators under study. These form the Early Childhood Epilepsy Severity Scale. The predictive validity of the E-Chess was satisfactory. The E-Chess provides an epilepsy severity score that can be easily used to assess epilepsy severity in tuberous sclerosis and would merit evaluation in other early onset childhood epilepsies.

LEGO therapy and the social use of language programme: an evaluation of two social skills interventions for children with high functioning autism and Asperger Syndrome.

LEGO therapy and the Social Use of Language Programme (SULP) were evaluated as social skills interventions for 6-11 year olds with high functioning autism and Asperger Syndrome. Children were matched on CA, IQ, and autistic symptoms before being randomly assigned to LEGO or SULP. Therapy occurred for 1 h/week over 18 weeks. A no-intervention control group was also assessed. Results showed that the LEGO therapy group improved more than the other groups on autism-specific social interaction scores (Gilliam Autism Rating Scale). Maladaptive behaviour decreased significantly more in the LEGO and SULP groups compared to the control group. There was a non-significant trend for SULP and LEGO groups to improve more than the no-intervention group in communication and socialisation skills.

Characterization of autism in young children with tuberous sclerosis complex.

Both cognitive impairment and autism are common in the tuberous sclerosis complex, but the relationship between the 2 diagnoses has not been formally explored. The authors evaluated 20 clinic-referred children with tuberous sclerosis complex at ages 18, 24, 36, and 60 months and classified them as autism, autism spectrum disorder, or normal on the basis of the Autism Diagnostic Observation Schedule. Using the Mullen Scale of Early Learning, cognitive function in each subgroup was assessed. The authors then analyzed the subscores of the Autism Diagnostic Observation Schedule in children with autism. Children with autism showed significantly more global cognitive impairment than those without autism. In addition, all children had some baseline cognitive impairment and the majority had deficits in play scores. The authors conclude that clinic-referred children with tuberous sclerosis complex and autism are at considerable risk for cognitive impairment. These characteristics may help to guide more tailored services for these high-risk children.

Trauma-focused cognitive behaviour therapy versus treatment as usual for post traumatic stress disorder (PTSD) in young children aged 3 to 8 years: study protocol for a randomised controlled trial.

BACKGROUND: Following horrific or life-threatening events approximately 10 to 15% of young children develop post traumatic stress disorder (PTSD). The symptoms of this disorder are distressing - nightmares, flashbacks, anger outbursts and disturbed play. These symptoms cause major disruption to a child's functioning and, if left untreated, can persist for many years. As yet, there are no established empirically-validated treatments for PTSD in young children. Trauma-focused cognitive behaviour therapy (TF-CBT) is a psychological intervention that is effective in treating the disorder in older children (8 to 12 years), adolescents and adults. This study examines TF-CBT adapted for children aged between 3 and 8 years. METHODS/DESIGN: This protocol describes a two-arm exploratory randomised controlled trial comparing TF-CBT to treatment as usual (TAU) in children aged 3 to 8 years with a principal diagnosis of PTSD following a single-event discrete trauma. Using a half-crossover design, 44 participants will be randomly allocated to receive the intervention or to receive TAU. Those allocated to TAU will be offered TF-CBT at the end of the 'treatment' period (approximately 12 weeks) if still indicated. The primary outcome is PTSD diagnosis according to DSM-5 criteria for children 6 years and younger at post-treatment. Secondary outcomes include effects on co-morbid diagnoses and changes in emotion and trauma symptoms at each of the follow-up points (post-treatment, 3-months, 12-months). Additionally, broader efficacy will be considered with regard to treatment feasibility, acceptability and service utilisation. The key targets of the intervention are trauma memory, the interpretation of the meaning of the event, and the management of symptoms. DISCUSSION: This is the first European trial to examine the efficacy of TF-CBT in alleviating PTSD in very young children. As well as providing much-needed data on the utility of the intervention, this exploratory trial will also allow us to gather important information about the feasibility of delivering the treatment in UK National Health Service (NHS) settings, and its acceptability to the children and their families. This study will highlight aspects of the intervention that need improvement or modification in preparation for a full-scale evaluation in a larger sample. TRIAL REGISTRATION: ISRCTN35018680 , registered on 18 November 2013.

Reliability of self, parental, and researcher measurements of head circumference.

BACKGROUND: The measurement of head circumference (HC) is widely used in clinical and research settings as a proxy of neural growth. Although it could aid data collection, no studies have explored either the reliability of adult self-measurements or parental measurements of young children. This study therefore aimed to examine whether adult self and parental measurement of HC constitute reliable data. FINDINGS: A total of 57 adults (32 male) were asked to measure their HC twice following written instructions (adult self-measurement). These measures were compared to those of a researcher independently measuring the same participant's HC twice. Additionally, mothers of 25 children (17 male) were also asked to measure their child's HC (parental measure), and again this was compared to researcher measurements of the child's HC. The intraclass correlation coefficient between adult self- and researcher measurement was 0.84 and between parent and researcher measurement was 0.99. The technical error of measurement was also acceptable, within the range of a skilled anthropometrist. CONCLUSIONS: The high degree of agreement between researcher and adult self-measurement/parental measurement of HC demonstrates that these different assessors produce similarly reliable and reproducible data. This suggests adult self- and parental measurements can reliably be used for data collection to enable valid large-scale developmental and clinical studies of HC.

The Tuberous Sclerosis 2000 Study: presentation, initial assessments and implications for diagnosis and management.

AIMS: The Tuberous Sclerosis 2000 Study is the first comprehensive longitudinal study of tuberous sclerosis (TS) and aims to identify factors that determine prognosis. Mode of presentation and findings at initial assessments are reported here. METHODS: Children aged 0-16 years newly diagnosed with TS in the UK were evaluated. RESULTS: 125 children with TS were studied. 114 (91%) met clinical criteria for a definite diagnosis and the remaining 11 (9%) had pathogenic TSC1 or TSC2 mutations. In families with a definite clinical diagnosis, the detection rate for pathogenic mutations was 89%. 21 cases (17%) were identified prenatally, usually with abnormalities found at routine antenatal ultrasound examination. 30 cases (24%) presented before developing seizures and in 10 of these without a definite diagnosis at onset of seizures, genetic testing could have confirmed TS. 77 cases (62%) presented with seizures. Median age at recruitment assessment was 2.7 years (range: 4 weeks-18 years). Dermatological features of TS were present in 81%. The detection rate of TS abnormalities was 20/107 (19%) for renal ultrasound including three cases with polycystic kidney disease, 51/88 (58%) for echocardiography, 29/35 (83%) for cranial CT and 95/104 (91%) for cranial MRI. 91% of cases had epilepsy and 65% had intellectual disability (IQ<70). CONCLUSIONS: Genetic testing can be valuable in confirming the diagnosis. Increasing numbers of cases present prenatally or in early infancy, before onset of seizures, raising important questions about whether these children should have EEG monitoring and concerning the criteria for starting anticonvulsant therapy.

Biological markers of intellectual disability in tuberous sclerosis.

BACKGROUND: Intellectual disability (ID) is highly prevalent in tuberous sclerosis (TS). Putative neurobiological risk factors include indices of cortical tuber (CT) load and epilepsy. We have used univariate and multivariate analyses, including both CT and epilepsy measures as predictors, in an attempt to clarify the pattern of cross-sectional associations between these variables and ID in TS. METHOD: Forty-eight children, adolescents and young adults with TS were identified through regional specialist clinics. All subjects underwent thorough history taking and examination, and had brain magnetic resonance imaging (MRI) scans. The number and regional distribution of CTs was recorded. Subjects were assigned to one of nine ordered intellectual quotient (IQ) categories (range 130) using age-appropriate tests of intelligence. RESULTS: On univariate analyses, ID was significantly associated with both a history of infantile spasm (IS) (Z=-2.49, p=0.01) and total CT count (Spearman's rho=-0.30, p=0.04). When controlling for total CT count, the presence of CTs in frontal (regression coefficient=-2.43, p=0.02) and temporal (regression coefficient=-1.60, p=0.02) lobes was significantly associated with ID. In multivariate analyses the association between IS and ID was rendered insignificant by the inclusion of the presence of CTs in temporal and frontal lobes, both of which remained associated (p=0.05 and p=0.06 respectively) with ID. CONCLUSIONS: The presence of CTs in specific brain regions as opposed to a history of IS was associated with ID in TS. The significance of these findings is discussed in relation to previous work in TS, and the neural basis of intelligence.

Autistic regression associated with seizure onset in an infant with tuberous sclerosis.

We report here on a male diagnosed with tuberous sclerosis at 6 months of age. The child was treated with vigabatrin at age 6 months after an abnormal electroencephalogram but before onset of seizures. Vigabatrin was discontinued at age 13 months to avoid possible visual field defects. At 21 months, the child developed partial seizures with secondary generalization and infantile spasms. Standardized developmental assessments were performed at 12, 18, 24, 30, and 36 months of age. Cognitive and social development were normal until age 21 months and the onset of seizures. When assessed at 24 months, the child met criteria for autism and learning disability. This case indicates that the onset of epilepsy during an early stage in brain development can be associated with autistic regression and persistent developmental disorder. The case suggests the need to consider if possible visual field defects with vigabatrin outweigh the potentially deleterious effects of uncontrolled seizures.