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Aim To compare the neurodevelopment of children with unilateral cerebral palsy (CP) with middle cerebral artery (MCA) and periventricular venous infarctions (PVIs). Method In this cross‐sectional study, children with unilateral CP completed a neurological exam, unimanual Quality of Upper Extremity Skills Test, hand usage questionnaires, and IQ test. Neuroimaging was obtained from health records. Results Two hundred and forty‐five participants with unilateral CP had neuroimaging (151 [61.9%] male, ages 2–18y, median=7y 6mo, interquartile range [IQR]=6y 7mo, with 93.6% in Gross Motor Function Classification System level I/II and 78.8% in Manual Ability Classification System level I/II). Ninety‐seven (39.6%) had MCA injuries and 106 (43.3%) had periventricular white matter injuries, of which 48 (45.3%) were PVIs. Median Quality of Upper Extremity Skills Test for the MCA group was 49.2 (IQR=55.8), PVI 79.9 (IQR=23.6) (Mann–Whitney U=988.50, p, Video Podcast: https://youtu.be/79w_s82qhr0

In a cohort of kindergarten children in Ontario, Canada with Autism Spectrum Disorder (ASD) (n = 1522), we tested the association of age at ASD diagnosis and characteristics of (1) the child’s primary care provider and, (2) the child using health administrative databases. We tested the association of primary care practice model and time from developmental delay identification to age at ASD diagnosis. Older age of diagnosis was associated with provider foreign training (vs. domestic) (adjusted Hazard Ratio [aHR] 1.17, 95% CI 1.03, 1.33) but not sex, care model, and years of practice. After developmental delay identification, children with paediatricians had longer time to diagnosis than children with providers in care models (aHR 0.68, 95% CI 0.54, 0.86). Findings can be used to inform primary care provider ASD training.

Hemiplegic cerebral palsy (CP), the most common subtype, is characterized by high levels of mobility. Despite this, children with hemiplegic CP can face challenges functioning in and adapting to situations of everyday life. The purpose of this cross-sectional study (Hemi-NET database) was to identify factors associated with adaptive behaviour in 59 children with hemiplegic CP (ages 4–18; GMFCS I-IV). Using multivariate regression analyses, the relationship between demographic, medical, and developmental factors and adaptive behaviour (measured by the Adaptive Skills Composite score of the BASC-2) was explored. Results indicate that 34% of children had impaired adaptive skills. An autism diagnosis and lower communication functioning were significantly associated with poorer adaptive skills (R2 = 0.42, F(4, 43) = 7.87, p

IntroductionYouth with brain-based disabilities (BBDs), as well as their parents/caregivers, often feel ill-prepared for the transfer from paediatric to adult healthcare services. To address this pressing issue, we developed the MyREADY TransitionTM BBD App, a patient-facing e-health intervention. The primary aim of this randomised controlled trial (RCT) was to determine whether the App will result in greater transition readiness compared with usual care for youth with BBD. Secondary aims included exploring the contextual experiences of youth using the App, as well as the interactive processes of youth, their parents/caregivers and healthcare providers around use of the intervention.Methods and analysisWe aimed to randomise 264 youth with BBD between 15 and 17 years of age, to receive existing services/usual care (control group) or to receive usual care along with the App (intervention group). Our recruitment strategy includes remote and virtual options in response to the current requirements for physical distancing due to the COVID-19 pandemic. We will use an embedded experimental model design which involves embedding a qualitative study within a RCT. The Transition Readiness Assessment Questionnaire will be administered as the primary outcome measure. Analysis of covariance will be used to compare change in the two groups on the primary outcome measure; analysis will be intention-to-treat. Interviews will be conducted with subsets of youth in the intervention group, as well as parents/caregivers and healthcare providers.Ethics and disseminationThe study has been approved by the research ethics board of each participating site in four different regions in Canada. We will leverage our patient and family partnerships to find novel dissemination strategies. Study findings will be shared with the academic and stakeholder community, including dissemination of teaching and training tools through patient associations, and patient and family advocacy groups.Trial registration numberNCT03852550.

Fibroblast growth factor homologous factors (FHFs) are intracellular proteins which regulate voltage-gated sodium (Na(v)) channels in the brain and other tissues. FHF dysfunction has been linked to neurological disorders including epilepsy. Here, we describe two sibling pairs and three unrelated males who presented in infancy with intractable focal seizures and severe developmental delay. Whole-exome sequencing identified hemi- and heterozygous variants in the N-terminal domain of the A isoform of FHF2 (FHF2A). The X-linked FHF2 gene (also known as FGF13) has alternative first exons which produce multiple protein isoforms that differ in their N-terminal sequence. The variants were located at highly conserved residues in the FHF2A inactivation particle that competes with the intrinsic fast inactivation mechanism of Na(v) channels. Functional characterization of mutant FHF2A co-expressed with wild-type Na(v)1.6 (SCN8A) revealed that mutant FHF2A proteins lost the ability to induce rapid-onset, long-term blockade of the channel while retaining pro-excitatory properties. These gain-of-function effects are likely to increase neuronal excitability consistent with the epileptic potential of FHF2 variants. Our findings demonstrate that FHF2 variants are a cause of infantile-onset developmental and epileptic encephalopathy and underline the critical role of the FHF2A isoform in regulating Na(v) channel function.

There is limited knowledge about the relationship between neighbourhood socioeconomic status (SES) and development of kindergarten children with ASD. The primary objective of this study was to determine the association between neighbourhood SES and developmental vulnerability of kindergarten children with ASD while controlling for family SES across 10 provinces and territories in Canada. This study used data from a population level database of child development in kindergarten, collected with the Early Development Instrument (EDI). The EDI covers five broad domains of developmental health: physical health and well-being, social competence, emotional maturity, language and cognitive development, and communication skills and general knowledge. Neighbourhood SES was assessed with an SES index created using 10 variables from the 2011 Canadian Census and 2010 Taxfiler data. Family SES was assessed using 4 variables from the 2016 Canadian Census. Descriptive statistics and regression-based models were used in this study. Multilevel binary logistic regression analyses were used to examine the association between neighbourhood SES and child developmental vulnerability (yes/no), at the individual level, while controlling for family SES, demographic characteristics, and neighbourhood clustering. The association between neighbourhood SES and child developmental vulnerability at the individual level, while controlling for family SES and demographic characteristics was examined with binary single level logistic regression analyses. Multivariable linear regression analyses were used to examine the association between neighbourhood SES and developmental vulnerability at the neighbourhood level (% of kindergarten children with ASD demonstrating developmental vulnerability in a neighbourhood). In Ontario, British Columbia, Manitoba, and Newfoundland and Labrador, higher neighbourhood SES was associated with lower likelihood of developmental vulnerability. In Nova Scotia, higher neighbourhood SES was associated with higher likelihood of vulnerability in the social competence and communication skills and general knowledge domains. These findings emphasize the importance of addressing neighbourhood deprivation to support the development of children with ASD. Additionally, the inconsistency highlights the importance of examining the mechanisms through which neighbourhood SES impacts development of these children on a provincial basis.

Children and adolescents with cerebral palsy often receive botulinum toxin A (BoNT-A) to manage hypertonia. This qualitative study aimed to describe and categorize BoNT-A effects that parents observed using the WHO’s International Classification of Functioning, Disability and Health (ICF) framework. An interpretive description methodology was used; semi-structured interviews were conducted with 15 parents of nonambulatory young people with cerebral palsy (mean age 10.2 years, SD 3.9, 7 males) who received BoNT-A. Parents reported BoNT-A effects on each ICF category. Through interpretive description, an overall theme emerged: “finding the right path to do what is best.” Five subthemes included (1) Parents’ hopes, (2) Parents’ goals for their child, (3) Parents’ learning what works, (4) Parents’ reflections, and (5) Parents’ destination. This study provides insights into parents’ journeys of how they learned about BoNT-A effects in their child, which helped them to identify goals for future treatment.

Primary Subject area Neonatal-Perinatal Medicine Background Preterm infants are at high risk of experiencing a range of impairments that may contribute to long-term challenges such as neurocognitive deficits. Physicians are often expected to give an outlook on future developmental outcomes of high-risk infants, often before sufficient time has elapsed to observe whether that particular child will demonstrate neurologic recovery from the initial injury. Clinicians often struggle with communicating this information, especially a poor prognosis, because of the worry about how these conversations affect families and their future expectations of the child. Objectives Our aim was to capture parents' retrospective perceptions of how their infant’s prognosis was communicated to them during their NICU stay. Design/Methods Semi-structured interviews were conducted over the phone with parents of former preterm infants with a birthweight below 1500 grams or parents of term infants who have sustained HIE requiring cooling. Parents were invited to participate when their child was between 12-36 months old at the time of the interview, so that parents would be able to have a sense of their child’s development and possible impairments. The data was analyzed thematically, with particular focus around the discourse of communication and prognostication. Results Twenty-three interviews were conducted: 20 with the biological mother, two with both biological parents, and one with the biological father. The average length of the interviews was 30 minutes. The main themes that recurred in the interviews included parental loss of control, needing to prepare for the unexpected, the value of shared decision making between the health care practitioners and parents, recognition and conveyance of uncertainty by the physician, and the importance of celebrating the present. Above all, a recurring theme mentioned by the majority of interviewees was the power of hope. While wanting to receive transparent and honest updates, parents felt strongly that giving them realistic hope was of utmost importance. Conclusion Although clinicians often feel pressured to deliver answers, parents found it helpful when clinicians acknowledged and explained the uncertainty that surrounds prognostication. While healthcare providers may feel the need to prepare parents for the worst, the importance of balancing this information with hope and positivity is what families remember and value years after the prognosis was given.

BACKGROUND: We lack knowledge of the developmental profiles of different brain injuries in hemiplegic cerebral palsy (HCP). This is important because children with specific injury patterns may respond differently to rehabilitation interventions. OBJECTIVES: To assess the relative proportion of brain injury patterns in HCP and compare the developmental profile of children with middle cerebral artery (MCA) and periventricular venous infarctions (PVI). DESIGN/METHODS: Children aged 2–18 years with a diagnosis of HCP were recruited from 9 children’s rehabilitation hospitals and informed consent was obtained. Developmental and neuroimaging information were collected from 6 sources: 1) data extraction from the health record, 2) brain imaging categorized by a neuroradiologist, 3) administration of the Quality of Upper Extremity Skills Test (QUEST) and classification of Gross Motor Function Classification System (GMFCS) and Manual Ability Classification System (MACS) by an occupational therapist, 4) child/parent questionnaires on hand usage: the Children’s Hand-use Experience Questionnaire (CHEQ) or Pediatric Upper Extremity Motor Activity Log (PMAL), 5) physician-administered sensory exam and 6) full scale intelligence quotient (IQ). Two groups comprising the most prevalent brain injury patterns were compared using a cross-sectional study design. RESULTS: Of 321 recruited, 246 (76.6%) had neuroimaging and were included in the analyses. The mean age was 8.30± 4.28, GMFCS I (n=181, 77.0%) and II (n=39, 16.6%), MACS I (n=82, 35.3%), II (n= 101, 43.5%). Neuroimaging revealed MCA infarctions (n=98, 39.8%), periventricular white matter lesions (n=110, 44.7%) of which periventricular venous infarction (PVI) was present in n=41, (16.7%), miscellaneous (n=8, 3.3%), unilateral malformations (n=19, 7.7%), non-MCA arterial infarctions (n=3, 1.2%), and normal imaging (n=8, 3.3%). Comparing PVI to MCA, the QUEST total score was higher in PVI, with 79.43±16.96 compared to 49.79±31.39 in MCA (t = 5.48, p value

Purpose Hemiplegia is a subtype of cerebral palsy (CP) in which one side of the body is affected. Our earlier study of unselected children with CP demonstrated de novo and clinically relevant rare inherited genomic copy-number variations (CNVs) in 9.6% of participants. Here, we examined the prevalence and types of CNVs specifically in hemiplegic CP. Methods We genotyped 97 unrelated probands with hemiplegic CP and their parents. We compared their CNVs to those of 10,851 population controls, in order to identify rare CNVs (

Mutations of genes within the phosphatidylinositol-3-kinase (PI3K)-AKT-MTOR pathway are well known causes of brain overgrowth (megalencephaly) as well as segmental cortical dysplasia (such as hemimegalencephaly, focal cortical dysplasia and polymicrogyria). Mutations of the AKT3 gene have been reported in a few individuals with brain malformations, to date. Therefore, our understanding regarding the clinical and molecular spectrum associated with mutations of this critical gene is limited, with no clear genotype-phenotype correlations. We sought to further delineate this spectrum, study levels of mosaicism and identify genotype-phenotype correlations of AKT3-related disorders. We performed targeted sequencing of AKT3 on individuals with these phenotypes by molecular inversion probes and/or Sanger sequencing to determine the type and level of mosaicism of mutations. We analysed all clinical and brain imaging data of mutation-positive individuals including neuropathological analysis in one instance. We performed ex vivo kinase assays on AKT3 engineered with the patient mutations and examined the phospholipid binding profile of pleckstrin homology domain localizing mutations. We identified 14 new individuals with AKT3 mutations with several phenotypes dependent on the type of mutation and level of mosaicism. Our comprehensive clinical characterization, and review of all previously published patients, broadly segregates individuals with AKT3 mutations into two groups: patients with highly asymmetric cortical dysplasia caused by the common p.E17K mutation, and patients with constitutional AKT3 mutations exhibiting more variable phenotypes including bilateral cortical malformations, polymicrogyria, periventricular nodular heterotopia and diffuse megalencephaly without cortical dysplasia. All mutations increased kinase activity, and pleckstrin homology domain mutants exhibited enhanced phospholipid binding. Overall, our study shows that activating mutations of the critical AKT3 gene are associated with a wide spectrum of brain involvement ranging from focal or segmental brain malformations (such as hemimegalencephaly and polymicrogyria) predominantly due to mosaic AKT3 mutations, to diffuse bilateral cortical malformations, megalencephaly and heterotopia due to constitutional AKT3 mutations. We also provide the first detailed neuropathological examination of a child with extreme megalencephaly due to a constitutional AKT3 mutation. This child has one of the largest documented paediatric brain sizes, to our knowledge. Finally, our data show that constitutional AKT3 mutations are associated with megalencephaly, with or without autism, similar to PTEN-related disorders. Recognition of this broad clinical and molecular spectrum of AKT3 mutations is important for providing early diagnosis and appropriate management of affected individuals, and will facilitate targeted design of future human clinical trials using PI3K-AKT pathway inhibitors.

This retrospective cohort study reviewed set goals and their outcomes of children and adolescents with severe cerebral palsy who received botulinum toxin A in 2008 and 2009. Sixty children (36 male, mean age 9 years) were included. They received on average 4 (range 1-7) treatments, with the dosage varying between 20 and 400 units per treatment (3-21 U/kg/body weight). Mild transient side effects were reported in 12 of 242 treatments with botulinum toxin A. Treatment goals were related to lower limb function (82%), range of motion (68%), positioning (33%), upper limb function (33%), and facilitating ease of care in dressing (30%), toileting, and diapering (22%). The treatment goals were reached in 60% to 85% by report of the parent and child dyad. Our findings suggest that botulinum toxin A should be considered as a treatment option in patients with cerebral palsy within Gross Motor Function Classification System levels IV and V.

Item does not contain fulltext Leigh syndrome (LS) is a progressive neurodegenerative disease caused by either mitochondrial or nuclear DNA mutations resulting in dysfunctional mitochondrial energy metabolism. Mutations in genes encoding for subunits of the respiratory chain or assembly factors of respiratory chain complexes are often documented in LS cases. Nicotinamide adenine dinucleotide (NADH):ubiquinone oxidoreductase (complex I) enzyme deficiencies account for a significant proportion of mitochondrial disorders, including LS. In an attempt to expand the repertoire of known mutations accounting for LS, we describe the clinical, radiological, biochemical and molecular data of six patients with LS found to have novel mutations in two complex I subunits (NDUFV1 and NDUFS2). Two siblings were homozygous for the previously undescribed R386C mutation in NDUFV1, one patient was a compound heterozygote for the R386C mutation in NDUFV1 and a frameshift mutation in the same gene, one patient was a compound heterozygote for the R88G and R199P mutations in NDUFV1, and two siblings were compound heterozygotes for an undescribed E104A mutation in NDUFS2. After the novel mutations were identified, we employed prediction models using protein conservation analysis (SIFT, PolyPhen and UCSC genome browser) to determine pathogenicity. The R386C, R88G, R199P, and E104A mutations were found to be likely pathogenic, and thus presumably account for the LS phenotype. This case series broadens our understanding of the etiology of LS by identifying new molecular defects that can result in complex I deficiency and may assist in targeted diagnostics and/or prenatal diagnosis of LS in the future.

Using resting state functional magnetic resonance imaging (MRI), we aim to understand the neurologic basis of improved function in children with hemiplegic cerebral palsy treated with constraint-induced movement therapy. Eleven children including 4 untreated comparison subjects diagnosed with hemiplegic cerebral palsy were recruited from 3 clinical centers. MRI and clinical data were gathered at baseline and 1 month for both groups, and 6 months later for the case group only. After constraint therapy, the sensorimotor resting state network became more bilateral, with balanced contributions from each hemisphere, which was sustained 6 months later. Sensorimotor resting state network reorganization after therapy was correlated with a change in the Quality of Upper Extremity Skills Test score at 1 month (r = 0.79, P = .06), and Canadian Occupational Performance Measure scores at 6 months (r = 0.82, P = .05). This clinically correlated resting state network reorganization provides further evidence of the neuroplastic mechanisms underlying constraint-induced movement therapy.

Objective. Between October and November 2003, several infants with encephalopathy were hospitalized in pediatric intensive care units in Israel. Two died of cardiomyopathy. Analysis of the accumulated data showed that all had been fed the same brand of soy-based formula (Remedia Super Soya 1), specifically manufactured for the Israeli market. The source was identified on November 6, 2003, when a 5.5-month-old infant was admitted to Sourasky Medical Center with upbeat nystagmus, ophthalmoplegia, and vomiting. Wernicke's encephalopathy was suspected, and treatment with supplementary thiamine was started. His condition improved within hours. Detailed history revealed that the infant was being fed the same formula, raising suspicions that it was deficient in thiamine. The formula was tested by the Israeli public health authorities, and the thiamine level was found to be undetectable ( Methods. After the index case, an additional 8 infants were identified in our centers by medical history, physical examination, and laboratory testing. The group consisted of 6 male and 3 female infants aged 2 to 12 months. All were assessed with the erythrocyte transketolase activity assay, wherein the extent of thiamine deficiency is expressed in percentage stimulation compared with baseline (thiamine pyrophosphate effect [TPPE]). Normal values range from 0% to 15%; a value of 15% to 25% indicates thiamine deficiency, and >25% indicates severe deficiency. Blood lactate levels (normal: 0.5–2 mmol/L) were measured in 6 infants, cerebrospinal fluid lactate in 2 (normal: 0.5–2 mmol/L), and blood pyruvate in 4 (normal: 0.03–0.08 mmol/L). The diagnostic criteria for thiamine deficiency were abnormal transketolase activity and/or unexplained lactic acidosis. Treatment consisted of intramuscular thiamine 50 mg/day for 14 days combined with a switch to another infant formula. Results. Early symptoms were nonspecific and included mainly vomiting (n = 8), lethargy (n = 7), irritability (n = 5), abdominal distension (n = 4), diarrhea (n = 4), respiratory symptoms (n = 4), developmental delay (n = 3), and failure to thrive (n = 2). Infection was found in all cases. Six infants were admitted with fever. One patient had clinical dysentery and group C Salmonella sepsis; the others had mild infection: acute gastroenteritis (n = 2); upper respiratory infection (n = 2); and bronchopneumonia, acute bronchitis, and viral infection (n = 1 each). Two infants were treated with antibiotics. Three infants had neurologic symptoms of ophthalmoplegia with bilateral abduction deficit with or without upbeat nystagmus. All 3 had blood lactic acidosis, and 2 had high cerebrospinal fluid lactate levels. Patient 1, our index case, was hospitalized for upbeat nystagmus and ophthalmoplegia, in addition to daily vomiting episodes since 4 months of age and weight loss of 0.5 kg. Findings on brain computed tomography were normal. Blood lactate levels were high, and TPPE was 37.8%. Brain magnetic resonance imaging (MRI) revealed no abnormalities. Patient 2, who presented at 5 months with lethargy, vomiting, grunting, and abdominal tenderness, was found to have intussusception on abdominal ultrasound and underwent 2 attempts at reduction with air enema several hours apart. However, the lethargy failed to resolve and ophthalmoplegia appeared the next day, leading to suspicions of Wernicke's encephalopathy. Laboratory tests showed severe thiamine deficiency (TPPE 31.2%). In patients 1 and 2, treatment led to complete resolution of symptoms. The third infant, a 5-month-old girl, was admitted on October 10, 2003, well before the outbreak was recognized, with vomiting, fever, and ophthalmoplegia. Her condition deteriorated to seizures, apnea, and coma. Brain MRI showed a bilateral symmetrical hyperintense signal in the basal ganglia, mamillary bodies, and periaqueductal gray matter. Suspecting a metabolic disease, vitamins were added to the intravenous solution, including thiamine 250 mg twice a day. Clinical improvement was noted 1 day later. TPPE assay performed after treatment with thiamine was started was still abnormal (17.6%). Her formula was substituted after 4 weeks, after the announcement about the thiamine deficiency. Although the MRI findings improved 5 weeks later, the infant had sequelae of ophthalmoplegia and motor abnormalities and is currently receiving physiotherapy. All 3 patients with neurologic manifestations were fed exclusively with the soy-based formula for 2 to 3.5 months, whereas the others had received solid food supplements. Longer administration of the formula (ie, chronic thiamine deficiency) was associated with failure to thrive. For example, one 12-month-old girl who received the defective formula for 8 months presented with refusal to eat, vomiting, failure to thrive (75th to 15%) were noted in 8 infants, 3 male and 5 female, all >1 year old, who were receiving solid food supplements. Although their parents failed to notice any symptoms, irritability, lethargy, vomiting, anorexia, failure to thrive, and developmental delay were documented by the examining physicians. None had signs of neurologic involvement. Treatment consisted of oral thiamine supplements for 2 weeks. Conclusions. Clinician awareness of the possibility of thiamine deficiency even in well-nourished infants is important for early recognition and prevention of irreversible brain damage. Therapy with large doses of thiamine should be initiated at the earliest suspicion of vitamin depletion, even before laboratory evidence is available and before neurologic or cardiologic symptoms appear.

Our technical ability to diagnose fetal anomalies of the central nervous system by ultrasonography and by fetal magnetic resonance imaging far exceeds our current knowledge of their possible neurodevelopmental implications later in life. This limitation often makes obstetric and clinical decisions very difficult. We retrospectively reviewed the ultrasonographic records of 6220 women who had been followed up at two large medical centers between 1994 and 1999. One hundred and sixty (2.6%) women had abnormal fetal central nervous system findings. The neurodevelopmental outcome of these children was assessed by a telephone interview with the parents. Small cerebellar size was the most frequent anomaly, followed by isolated mild ventriculomegaly and isolated choroid plexus pathology. Suboptimal neurodevelopmental outcome was found in 24% of children with isolated ventriculomegaly and in 9% with choroid plexus pathology. In the group of children with a "small cerebellum," suboptimal neurodevelopment was found in 19%. The measurement of transcerebellar diameter in respect to its developmental implication is, to our knowledge, described here for the first time. We believe that cerebellar measurements and their possible neurocognitive implications should be an integral part of future studies. ( J Child Neurol 2004;19:435-438).

Objective Velocardiofacial syndrome (VCFS) is the most common multiple anomaly disorder associated with palatal clefting. Cytogenetic hemizygous deletion of 22q11 region is found in 80% of patients. The frequency of 22q11 deletion in patients presenting with isolated palatal anomalies has not been fully assessed. Our objective was to determine the frequency of the deletion in patients with isolated palatal anomalies. Design Patients were referred because of velopharyngeal insufficiency because of isolated congenital palatal anomalies. Diagnosis of palatal anomalies was confirmed by videonasopharyngoscopy, multiview videofluoroscopy and cephalometry. Other clinical findings suggestive of VCFS were sought, and subjects with these characteristics were excluded from the study. Peripheral blood samples from all patients were analyzed cytogenetically utilizing fluorescent in situ hybridization for the 22q11 region. Results Thirty-eight patients aged 3 to 31 years were included in the study. Nine had cleft palate, 7 cleft lip and palate, 10 overt and 11 occult submucous cleft palate, and 1 had a deep nasopharynx. No deletion of 22q11 region was detected in any of the evaluated patients. Conclusions A routine screening for the 22q11 deletion in older children and adults presenting with an isolated palatal anomaly may not be required. Because other signs related to VCFS such as facial dysmorphism and behavioral or psychiatric disorders may evolve at an older age, young patients should be followed up and reevaluated for additional relevant symptoms that may lead to deletion evaluation. In light of the fact that the current literature is inconsistent, the relative small size of this study and the significant consequences of missed 22q11.2 deletion, more information is needed before definitive recommendations can be made.

The aim was to identify neuroimaging predictors of clinical improvements following constraint-induced movement therapy. Resting state functional magnetic resonance and diffusion tensor imaging data was acquired in 7 children with hemiplegic cerebral palsy. Clinical and magnetic resonance imaging (MRI) data were acquired at baseline and 1 month later following a 3-week constraint therapy regimen. A more negative baseline laterality index characterizing an atypical unilateral sensorimotor resting state network significantly correlated with an improvement in the Canadian Occupational Performance Measure score (r = –0.81, P = .03). A more unilateral network with decreased activity in the affected hemisphere was associated with greater improvements in clinical scores. Higher mean diffusivity in the posterior limb of the internal capsule of the affect tract correlated significantly with improvements in the Jebsen-Taylor score (r = –0.83, P = .02). Children with more compromised networks and tracts improved the most following constraint therapy.

AIM Optimizing movement quality is a common rehabilitation goal for children with cerebral palsy (CP). The new Quality Function Measure (QFM) – a revision of the Gross Motor Performance Measure (GMPM) – evaluates five attributes: Alignment, Co-ordination, Dissociated movement, Stability, and Weight-shift, for the Gross Motor Function Measure (GMFM) Stand and Walk/Run/Jump items. This study evaluated the reliability and discriminant validity of the QFM. METHOD Thirty-three children with CP (17 females, 16 males; mean age 8y 11mo, SD 3y 1mo; Gross Motor Function Classification System [GMFCS] levels I [n=17], II [n=7], III [n=9]) participated in reliability testing. Each did a GMFM Stand/Walk assessment, repeated 2 weeks later. Both GMFM assessments were videotaped. A physiotherapist assessor pair independently scored the QFM from an assigned child’s GMFM video. GMFM data from 112 children. That is, (GMFCS I [n=38], II [n=27], III [n=47]) were used for discriminant validity evaluation. RESULTS QFM mean scores varied from 45.0% (SD 27.2; Stability) to 56.2% (SD 27.5; Alignment). Reliability was excellent across all attributes: intraclass correlation coefficients (ICCs) ≥0.97 (95% confidence intervals [CI] 0.95–0.99), interrater ICCs ≥0.89 (95% CI 0.80–0.98), and test–retest ICCs ≥0.90 (95% CI 0.79–0.99). QFM discriminated qualitative attributes of motor function among GMFCS levels (maximum p

Hyperkinetic movements are unwanted or excess movements that are frequently seen in children with neurologic disorders. They are an important clinical finding with significant implications for diagnosis and treatment. However, the lack of agreement on standard terminology and definitions interferes with clinical treatment and research. We describe definitions of dystonia, chorea, athetosis, myoclonus, tremor, tics, and stereotypies that arose from a consensus meeting in June 2008 of specialists from different clinical and basic science fields. Dystonia is a movement disorder in which involuntary sustained or intermittent muscle contractions cause twisting and repetitive movements, abnormal postures, or both. Chorea is an ongoing random-appearing sequence of one or more discrete involuntary movements or movement fragments. Athetosis is a slow, continuous, involuntary writhing movement that prevents maintenance of a stable posture. Myoclonus is a sequence of repeated, often non-rhythmic, brief shock-like jerks due to sudden involuntary contraction or relaxation of one or more muscles. Tremor is a rhythmic back-and-forth or oscillating involuntary movement about a joint axis. Tics are repeated, individually recognizable, intermittent movements or movement fragments that are almost always briefly suppressible and are usually associated with awareness of an urge to perform the movement. Stereotypies are repetitive, simple movements that can be voluntarily suppressed. We provide recommended techniques for clinical examination and suggestions for differentiating between the different types of hyperkinetic movements, noting that there may be overlap between conditions. These definitions and the diagnostic recommendations are intended to be reliable and useful for clinical practice, communication between clinicians and researchers, and for the design of quantitative tests that will guide and assess the outcome of future clinical trials.

Cerebral palsy, typically diagnosed in childhood, clearly continues into adulthood. This study describes the long-term medical, functional, educational, and psychosocial outcomes of people with cerebral palsy. Of the 203 people with cerebral palsy diagnosed and treated at the Child Development Center in Tel Aviv between 1975 and 1994, 163 (80%; age range 8-30 years, mean age 18.9 years, and median age 19 years) participated in a cross-sectional telephone survey. Half the respondents have chronic health problems: 78% report they experience gross motor disability, of whom 22% are wheelchair users; 30% to 50% need help in various activities of daily living; 35% have mental retardation; 79% completed 12 years or more of schooling; 78% live with their parents; 25% have served in the army; 23% have a driver’s license; and 23% work in competitive employment. The large majority is involved in varied leisure activities and report a high level of life satisfaction.

The medical, educational, and psychosocial outcomes of 3224 subjects (age range, 7-33 years; mean age, 20.06 years; SD, 5.74) diagnosed and treated in the Institute for Child Development in Tel Aviv between the years 1975 and 1994 were assessed by a telephone interview. Results indicate that only 9% of the subjects are seriously disabled, and 8% are mentally retarded. Over the years, subjects were referred to the Child Development Center at an increasingly younger age, probably reflecting greater professional and parental awareness of the importance of early intervention. The nature of interventions changed, so that physiotherapy, occupational therapy, and psychological guidance were more often provided. While more children were referred to special education at kindergarten, the percentage of those graduating from regular schools has increased. Most completed 12 years of schooling and successfully acquired full or partial matriculation certificates. As adults, most function independently; fulfill civic obligations, such as their army service; are fully employed; and express satisfaction with their life. These results suggest that children with developmental disabilities who receive early intervention are likely to be functionally independent and to be satisfied with their lives, although they continue to need medical services and require some government support. Further studies are essential to examine the correlation of specific risk factors and early interventions with outcome.

Background Thrombophilic risk factors play an important role in the pathogenesis of perinatal stroke and resultant cerebral palsy (CP). The association between thrombophilia and CP caused by etiologies other than stroke is undetermined. Methods We assessed three genetic thrombophilic markers (mutation of Factor V Leiden [FV G1691A], 677T polymorphism of thermolabile methylenetetrahydrofolate reductase [MTHFR] and G20210A mutation of the prothrombin gene) in 49 pediatric patients with non-stroke CP and compared the findings with 118 apparently healthy controls. CP in the study group was due to periventricular leukomalacia ( n =27), intraventricular hemorrhage ( n =9), hypoxic ischemic encephalopathy ( n =4), prematurity with no apparent complication ( n =8) and intrauterine growth retardation ( n =1). Twenty-five children had spastic diplegia, 20 had spastic quadriplegia and 4 had spastic hemiplegia. CP was graded as being severe in 26 children (53%). Results No significant difference in the prevalence of thrombophilic risk factors was found between the study and control groups. Twelve study children (24.5%) had at least one of the three thrombophilic mutations compared with 27 controls (23%). There was no significant difference in the prevalence of each thrombophilic risk factor in the various etiologic groups and in the subgroups of mild/severe CP and the control group. Conclusion These findings support the notion that thrombophilia neither contributes to the occurrence nor affects the clinical outcome and severity of non-stroke CP.

Muscle-related complaints and high creatine kinase (CK) blood levels have been reported in 16-51% of patients with acne treated with isotretinoin. It has been suggested that this retinoid and exercise have a synergistic effect on muscle. The presence of marked hyperCKemia during the treatment raises concern about rhabdomyolysis. The objective of this report was to evaluate the incidence, course and clinical significance of severe hyperCKemia in isotretinoin therapy for acne. Out of 442 patients on isotretinoin, we reviewed 7 patients (1.58%) with CK values above 5,000 IU/l. Only two of them had myalgia. Physical activity or intramuscular injection prior to blood testing was reported in 6 patients. CK values returned to normal within 2 weeks and all subjects except 2, completed treatment. In conclusion, marked hyperCKemia with or without muscle-related complaints in isotretinoin-treated patients with acne is a benign phenomenon.

Background:This study aims to assess current practices of Canadian physicians providing botulinum toxin-A (BoNT-A) treatments for children with hypertonia and to contrast these with international “best practice” recommendations, in order to identify practice variability and opportunities for knowledge translation.Methods:Thirteen Canadian physicians assembled to develop and analyze results of a cross-sectional electronic survey, sent to 50 physicians across Canada.Results:Seventy-eight percent (39/50) of physicians completed the survey. The most frequently identified assessment tools were Gross Motor Function Classification System, Modified Tardieu Scale and neurological examination. Goal-setting tools were infrequently utilized. Common indications for BoNT-A injections and the muscles injected were identified. Significant variability was identified in using BoNT-A for hip displacement associated with hypertonia. The most frequent adverse event reported was localized weakness; 54% reporting this “occasionally“ and 15% “frequently”. Generalized weakness, fatigue, ptosis, diplopia, dysphagia, aspiration, respiratory distress, dysphonia and urinary incontinence were reported rarely or never. For dosage, 52% identified 16 Units/kg body weight of Botox® as maximum. A majority (64%) reported a maximum 400 Units for injection at one time. For localization, electrical stimulation and ultrasound were used infrequently (38% and 19% respectively). Distraction was the most frequently used pain-management technique (64%).Conclusions:Canadian physicians generally adhere to international best practices when using BoNT-A to treat paediatric hypertonia. Two knowledge-translation opportunities were identified: use of individualized goal setting prior to BoNT-A and enhancing localization techniques. Physicians reported a good safety profile of BoNT-A in children.