To review recent developments in the understanding, diagnosis, and treatment of Sturge–Weber syndrome (SWS).
Members of the Brain Vascular Malformation Consortium Sturge–Weber National Workgroup contributed their expertise, to review the literature, and present promising directions for research.
The increasing number of reports dealing with SWS over the last decade reflects progress in the diagnosis and understanding of the neurological involvement. The proliferation of centers and advocacy groups to care for patients with SWS and to stimulate research has aided the development of new insights into the clinical manifestations and the pathophysiology of neurological progression, and the development of novel hypotheses to direct future research. Many key questions remain, but the tools and networks to answer them are being developed.
This review summarizes important new knowledge and presents new research directions that are likely to provide further insights, earlier diagnosis, improved treatments, and possibly, prevention of this syndrome.
To investigate the relationships among the Gross Motor Function Classification System (GMFCS), Manual Ability Classification System (MACS), and Communication Function Classification System (CFCS) in children with cerebral palsy (CP).
Using questionnaires describing each scale, mothers reported GMFCS, MACS, and CFCS levels in 222 children with CP aged from 2 to17 years (94 females, 128 males). Children were referred from pediatric developmental/behavioral, physiatry, and child neurology clinics, in the USA, for a case–control study of the etiology of CP. Pairwise relationships among the three systems were assessed using Spearman’s correlation coefficients (rs), stratifying by age and CP topographical classifications.
Correlations among the three functional assessments were strong or moderate. GMFCS levels were highly correlated with MACS levels (rs=0.69) and somewhat less so with CFCS levels (rs=0.47). MACS and CFCS were also moderately correlated (rs=0.54). However, many combinations of functionality were found. Of the 125 possible combinations of the three five-point systems, 62 were found in these data.
Use of all three classification systems provides a more comprehensive picture of the child’s function in daily life than use of any one alone. This resulting functional profile can inform both clinical and research purposes.
Dysautonomia after brain injury is a diagnosis based on fever, tachypnea, hypertension, tachycardia, diaphoresis, and/or dystonia. It occurs in 8 to 33% of brain-injured adults and is associated with poor outcome. We hypothesized that brain-injured children with dysautonomia have worse outcomes and prolonged rehabilitation, and sought to determine the prevalence of dysautonomia in children and to characterize its clinical features.
We developed a database of children (n=249, 154 males, 95 females; mean (SD) age 11y 10mo [5y 7mo]) with traumatic brain injury, cardiac arrest, stroke, infection of the central nervous system, or brain neoplasm admitted to The Children’s Institute of Pittsburgh for rehabilitation between 2002 and 2009. Dysautonomia diagnosis, injury type, clinical signs, length of stay, and Functional Independence Measure for Children (WeeFIM) testing were extracted from medical records, and analysed for differences between groups with and without dysautonomia.
Dysautonomia occurred in 13% of children with brain injury (95% confidence interval 9.3–18.0%), occurring in 10% after traumatic brain injury and 31% after cardiac arrest. The combination of hypertension, diaphoresis, and dystonia best predicted a diagnosis of dysautonomia (area under the curve=0.92). Children with dysautonomia had longer stays, worse WeeFIM scores, and improved less on the score’s motor component (all p≤0.001).
Dysautonomia is common in children with brain injury and is associated with prolonged rehabilitation. Prospective study and standardized diagnostic approaches are needed to maximize outcomes.
Diffusion tensor imaging (DTI) was used to evaluate white matter architecture after preterm birth. The goals were (1) to compare white matter microstructure in two cohorts of preterm- and term-born children; and (2) within preterm groups, to determine if sex, gestational age, birthweight, white matter injury score from conventional magnetic resonance imaging (MRI), or IQ was associated with DTI measures.
Participants (n=121; 66 females, 55 males) were aged 9 to 16 years. They comprised 58 preterm children (site 1, n=25; and site 2, n=33) born at less than 36 weeks’ gestation (mean 29.4wks; birthweight 1289g) and 63 term children (site 1, n=40; site 2, n=23) born at more than 37 weeks’ gestation. DTI was analyzed using tract-based spatial statistics. Diffusion measures were fractional anisotropy, axial, radial, and mean diffusivity.
In no region of the white matter skeleton was fractional anisotropy lower in the preterm group at either site. Within the preterm groups, fractional anisotropy was significantly associated with white matter injury score, but not sex, gestational age, or birthweight. At site 1, fractional anisotropy was associated with IQ.
DTI contributes to understanding individual differences after preterm birth but may not differentiate a relatively high-functioning group of preterm children from a matched group of term-born children.
This study sought to examine the effect of environmental enrichment on the motor skills of children adopted from orphanage settings. We investigated balance and bilateral coordination skills in 33 internationally adopted postinstitutionalized children (16 males, 17 females; age range 8y 5mo–15y 10mo; mean age 10y 9mo; SD 2y 2mo) and compared them with 34 non-institutionalized children (21 males, 13 females; age range 8y 3mo–14y 10mo; mean age 11y 2mo; SD 2y 1mo) being raised in their birth families.
The children were individually administered the balance and bilateral coordination subtests of the Bruininks–Oseretsky Test of Motor Proficiency in a research laboratory. Parents completed questionnaires about developmental history, family environment, and orphanage care.
Postinstitutionalized children showed motor system delays compared with the non-institutionalized comparison children (postinstitutionalized balance mean 9.44, SD 5.92, comparison children balance mean 14.12, SD 4.39; postinstitutionalized bilateral coordination mean 11.97, SD 5.43, comparison children mean 19.97, SD 3.97). The length of time that children remained institutionalized before adoption predicted balance delays (b=−1.57, t=−2.33, p=0.027) and the severity of caregiving deprivation the children experienced correlated with bilateral coordination (r=−0.44, p=0.013).
These findings suggest that institutionalized settings do not provide the early life experiences needed for the development of age-level motor skills later in childhood and that simple environmental enrichment following adoption is not enough to remediate skills. Children who have experienced early institutional care may benefit from early identification and targeted intervention.
We aimed to investigate the contribution of disease stage and weight for age to the variability in psychomotor outcome observed among children with human immunodeficiency virus (HIV) infection.
This cross-sectional study involved 48 Kenyan children (20 females, 28 males) aged 6 to 35 months (mean 19.9mo SD 8.9) exposed prenatally to HIV. Two subgroups of HIV-exposed children were seen: those who were HIV-infected and those who were uninfected. The reference population was composed of 319 children (159 females, 160 males) aged 6–35 months, (mean age = 19 months, SD=8.43) randomly selected from the community. Disease stage varied from stage 1 to stage 3, reflecting progression from primary HIV infection to advanced HIV infection and acquired immune deficiency syndrome. A locally developed and validated measure, the Kilifi Developmental Inventory, was used to assess psychomotor development.
Using age-corrected psychomotor scores, a significant main effect of HIV status was observed (F(2,38.01)=7.89, p<0.001). Children in the HIV-infected group had lower mean psychomotor scores than the HIV-exposed children and the reference group. In the HIV-infected group, disease stage was a negative predictor and weight for age a positive predictor of psychomotor outcome.
Weight for age and disease stage provide viable, easily measurable benchmarks to specify when frequent developmental monitoring and psychomotor rehabilitation are required. Nutritional intervention and other measures aimed at slowing disease progression may delay the onset and severity of psychomotor impairment in the paediatric HIV population in Africa.
To define the prevalence and associations of behaviour disorder in children with epilepsy from a rural district of Tanzania by conducting a community-based case-control study.
Children aged 6-14 years old with active epilepsy (at least two unprovoked seizures in the last five years) were identified in a cross-sectional survey in Tanzania. Behaviour was assessed using the Rutter scale. Cases were compared with age-matched controls.
Behaviour disorder was diagnosed in 68/103 (66%) of children with epilepsy and 19/99 (19%) of controls. Disordered behaviour was significantly more common in cases than controls (univariate OR 8.2, 95% CI 4.3 – 15.6, p<0.001) and in cases, was associated with frequent seizures and poor scholastic attainment in controls. Attention problems were present in 48/91 (53%) children with epilepsy and 16/97 (17%) controls (univariate OR 5.7. 95% CI 2.9 – 11.1, p<0.001). In cases, attention problems were significantly more common in males and associated with frequent seizures.
Children with epilepsy in a rural area of sub-Saharan Africa have a high prevalence of behavioural disorders and attention problems. Frequent seizures were associated with both. Providing behaviour assessment and appropriate intervention programmes for children with epilepsy may reduce the burden of behaviour disorder in this setting.
epilepsy; Africa; children; behaviour; attention
Brain systems supporting higher cognitive and motor control develop in a parallel manner, dependent on functional integrity and maturation of related regions, suggesting neighbouring neural circuitry. Concurrent examination of motor and cognitive control can provide a window into neurological development. However, identification of performance-based measures that do not correlate with IQ has been a challenge.
Timed motor performance from the Physical and Neurological Examination of Subtle Signs and IQ were analysed in 136 children aged 6 to 16 (mean age 10y 2.6mo, SD 2y 6.4mo; 98 female, 38male) attending an outpatient neuropsychology clinic and 136 right-handed comparison individuals aged 6 to 16 (mean age 10y 3.1mo, SD 2y 6.1mo; 98 female, 38male). Timed activities – three repetitive movements (toe tapping, hand patting, finger tapping) and three sequenced movements (heel–toe tap, hand pronate/supinate, finger sequencing) each performed on the right and left – were included in exploratory factor analyses.
Among comparison individuals, factor analysis yielded two factors – repetitive and sequenced movements – with the sequenced factor significantly predictive of Verbal IQ (VIQ) (ΔR2=0.018, p=0.019), but not the repetitive factor (ΔR2=0.004, p=0.39). Factor analysis within the clinical group yielded two similar factors (repetitive and sequenced), both significantly predictive of VIQ, (ΔR2=0.028, p=0.015; ΔR2=0.046, p=0.002 respectively).
Among typical children, repetitive timed tasks may be independent of IQ; however, sequenced tasks share more variance, implying shared neural substrates. Among neurologically vulnerable populations, however, both sequenced and repetitive movements covary with IQ, suggesting that repetitive speed is more indicative of underlying neurological integrity.
The aim of this study was to compare total and regional cerebral volumes in children with isolated cerebellar malformations (CBMs) with those in typically developing children, and to examine the extent to which cerebellar volumetric reductions are associated with total and regional cerebral volumes.
This is a case–control study of children diagnosed with isolated CBMs. Each child was matched on age and sex to two typically developing children. Using advanced three-dimensional volumetric magnetic resonance imaging, the cerebrum was segmented into tissue classes and partitioned into eight regions. Analysis of variance was used to compare cerebral volumes between children with CBMs and comparison children, and linear regressions to examine the impact of cerebellar volume reduction on cerebral volumes.
Magnetic resonance imaging was performed at a mean age of 27 months in 20 children (10 males, 10 females) with CBMs and 40 typically developing children. Children with CBMs showed significantly smaller deep grey matter nuclei (p<0.001), subgenual white matter (p=0.03), midtemporal white matter (p=0.02), and inferior occipital grey matter (p=0.03) volumes than typically developing children. Greater cerebellar volumetric reduction in children with CBMs was associated with decreased total cerebral volume and deep grey matter nuclei (p=0.02), subgenual white/grey matter (p=0.001), midtemporal white (p=0.02) and grey matter (p=0.01), and parieto-occipital grey matter (p=0.004).
CBMs are associated with impaired regional cerebral growth, suggesting deactivation of principal cerebello-cerebral pathways.
Increased end-tidal carbon monoxide (ETCOc) and cytokines in preterm infants are related to bronchopulmonary dysplasia and intraventricular haemorrhages. The aim was to study the predictive value of ETCOc and cytokine levels for long-term outcome.
This study comprised 105 very preterm infants (57 males, 48 females; gestational age range 25wk 5d–31wk 4d; birthweight 610–2100g) who were admitted to a neonatal intensive care unit between 1 February and 31 December 2002. ETCOc, plasma tumour necrosis factor alpha (TNF-α) and interleukins (IL) 6 and 8, and malondialdehyde (MDA, a marker of lipid peroxidation), were measured at days 1, 3, and 5 of life and related to outcome at 3 years 6 months of age (Griffiths Mental Developmental Scales).
Of the 105 infants, 69 were eligible for follow-up (37 male; 32 female; bronchopulmonary dysplasia, n=12). ETCOc at 0 to 24 hours was higher in infants with adverse outcome (Griffiths developmental quotient <85, n=15) compared with favourable outcome (2.7 SD 0.7 vs 2.0 SD 0.5; p<0.05). MDA and cytokines did not differ between groups. Regression analysis with bootstrapping of independent variables (gestational age, birthweight, ETCOc, TNF-α, IL-6, IL-8, and bronchopulmonary dysplasia) showed that ETCOc was the only parameter that correlated with outcome. The sensitivity and negative predictive value of ETCOc for adverse outcome were 93% and 85% respectively.
Adverse neurodevelopmental outcome is associated with increased endogenous carbon monoxide. ETCOc less than 2.0ppm during the first day indicates a favourable outcome.
To increase awareness of sudden and unexpected death in Lesch-Nyhan disease (LND) and to explore its potential causes, we report the anteceding clinical features and laboratory evaluations of five males with LND who ultimately experienced sudden and unexpected death, along with three additional males who suffered serious respiratory events during life. The ages of patients ranged from 2 to 45 years. The cause of sudden death in LND appears to have a respiratory rather than a cardiogenic basis. All cases cannot be linked readily with a single respiratory process. Instead, different respiratory processes appear to operate in different cases. These may include aspiration, laryngospasm, central apnea, cyanotic breath-holding spells, and high cervical spine damage. Better recognition of these processes will help to guide appropriate workup and management that could include chest imaging, endoscopy of the airways, polysomnography, electroencephalogram, and brain and/or spine imaging.
Tubers are the most common brain lesions in tuberous sclerosis complex (TSC), and typically remain stable in size and appearance. We present the case of a young male with global developmental impairment and autistic features as well as multiple and mixed daily seizures. The patient had a prominent right frontal cortical tuber characterized by a calcified component, which changed on consecutive magnetic resonance imaging between the age of 4 and 11 years, at which time the patient underwent a lesionectomy. A poor long-term outcome is reported since the patient presents an intractable mixed seizure disorder status post-epilepsy surgery and no significant neuropsychological improvements. Histopathology findings show typical characteristics of tubers in TSC as well as numerous calcifications within the resected nodular lesion. This case supports the notion that tubers with calcified components are not necessarily static lesions and can change with time. Investigation of the relationship between the presence of calcification in tubers and epileptogenecity in a large group of patients would provide insights into the pathogenesis of the seizures and cognitive impairment and hopefully, eventually provide better treatment options for patients with TSC.
The aim of this study was to determine whether oral, tactile/kinaesthetic (T/K), or combined (oral + T/K) interventions enhance oral feeding performance and whether combined (oral + T/K) interventions have an additive/synergistic effect.
Seventy-five preterm infants (mean gestational age 29wk; standard error of the mean [SEM] 0.3wk; mean birthweight 1340.3g; SEM 52.5g; 49 males and 26 females) were randomly assigned to one of three intervention groups or a control group. The oral group received sensorimotor input to the oral structures, the T/K group received sensorimotor input to the trunk and limbs, and the combined (oral + T/K) group received both. The outcomes were time from introduction of nipple feeding to independent oral feeding (days), proficiency (intake in the first 5min, %), volume transfer (%), rate of transfer (ml/min), volume loss (%), and length of hospital stay (days).
Infants in the three intervention groups achieved independent oral feeding 9 to 10 days earlier than those in the control group (p<0.001; effect size 1.9–2.1). Proficiency (p≤0.002; effect size 0.7–1.4) at the time of one to two and three to five oral feedings per day, volume transfer (p≤0.001; effect size 0.8–1.1) at one to two, three to five, and six to eight oral feedings per day, and overall rate of transfer (p≤0.018; effect size 0.8–1.1) were greater, and overall volume losses were less (p≤0.007; effect size 0.9–1.1), than in the control group (p≤0.042). The combined (oral + T/K) group attained independent oral feeding at a significantly younger postmenstrual age than controls (p=0.020) and had clinically greater proficiency than the T/K group (p=0.020; effect size 0.7) and oral group (p=0.109; effect size 0.5). Length of hospital stay was not significantly different between groups (p=0.792; effect size 0.02–0.3).
Oral and T/K interventions accelerated the transition from introduction to independent oral feeding and enhanced oral feeding skills. T/K has beneficial effects beyond the specific targeted system. The combined sensorimotor intervention led to an additive/synergistic effect for proficiency, further benefiting this population.
The corticospinal tract (CST) is the principal motor control pathway for skilled movements. It has a protracted postnatal development, creating a protracted period of vulnerability to perinatal brain and spinal cord injury. Research has shown that the motor signs in cerebral palsy (CP) reflect the loss of CST connections as well as development of abnormal motor systems connections, especially between the developing CST and spinal motor circuits. In this paper, we discuss a feline model of CP that we have developed. The animals develop a pattern of abnormal CST connections that are remarkably similar to those seen in hemiplegic CP and visuomotor impairments. Using this model we devised neural activity-based therapeutic approaches to repair the abnormal CST connections and restore normal skilled movement control. Our studies stress that more active CST connections are better able to maintain strong synaptic connections with spinal motor circuits. We propose that perinatal trauma initiates a vicious cycle in which CST axons that are spared after an injury are at a disadvantage for maintaining spinal connections, leading to further reductions in connections and motor signs. If this is so, targeted activation of the spared CST might interrupt this process and lead to functional improvement.
The purpose of this study was to create and validate a Communication Function Classification System (CFCS) for children with cerebral palsy (CP) that can be used by a wide variety of individuals who are interested in CP. This paper reports the content validity, interrater reliability, and test–retest reliability of the CFCS for children with CP.
An 11-member development team created comprehensive descriptions of the CFCS levels, and four nominal groups comprising 27 participants critiqued these levels. Within a Delphi survey, 112 participants commented on the clarity and usefulness of the CFCS. Interrater reliability was completed by 61 professionals and 68 parents/relatives who classified 69 children with CP aged 2 to 18 years. Test–retest reliability was completed by 48 professionals who allowed at least 2 weeks between classifications. The participants who assessed the CFCS were all relevant stakeholders: adults with CP, parents of children with CP, educators, occupational therapists, physical therapists, physicians, and speech–language pathologists.
The interrater reliability of the CFCS was 0.66 between two professionals and 0.49 between a parent and a professional. Professional interrater reliability improved to 0.77 for classification of children older than 4 years. The test–retest reliability was 0.82.
The CFCS demonstrates content validity and shows very good test–retest reliability, good professional interrater reliability, and moderate parent–professional interrater reliability. Combining the CFCS with the Gross Motor Function Classification System and the Manual Ability Classification System contributes to a functional performance view of daily life for individuals with CP, in accordance with the World Health Organization’s International Classification of Functioning, Disability and Health.
To describe the development of context therapy, a new intervention approach designed for a randomized controlled trial.
Therapists were trained to change task and environmental factors to achieve parent-identified functional goals for children with cerebral palsy. Therapists did not provide any remediation strategies to change the abilities of the child. Theoretical constructs were developed using dynamic systems theory and the principles of family-centered care. A primary therapist model was used. A three-step intervention strategy was developed.
Therapists adhered to the treatment protocol. Parents participated in the development of both functional goals and intervention strategies.
A therapy approach focusing on changing the task and the environment rather than children’s impairments can be a viable treatment strategy and merits further investigation. The detailed description of the context therapy approach allows replication by both researchers and clinicians. Such intervention descriptions are an important methodological consideration in rehabilitation research.
This study evaluated the efficacy of a child-focused versus context-focused intervention in improving performance of functional tasks and mobility in young children with cerebral palsy.
A randomized controlled trial cluster research design enrolled 128 children (49 females, 79 males; age range 12mo to 5y 11mo; mean age 3y 6mo, SD −1y 5mo) who were diagnosed with cerebral palsy. Children across levels I to V on the Gross Motor Classification System (GMFCS) were included in the study. Children were excluded if there were planned surgical or medication changes during the intervention period. Therapists from 19 children's rehabilitation centers were block randomized (by occupational therapist or physical therapist) to a treatment arm. Children from consenting families followed their therapists into their assigned group. Children received child-focused (n=71) or context-focused intervention (n=57) over 6 months, returning to their regular therapy schedule and approach between 6 and 9 months. The primary outcome measure was the Pediatric Evaluation of Disability Inventory (PEDI). Secondary outcome measures included the Gross Motor Function Measure (GMFM-66), range of motion of hip abduction, popliteal angle and ankle dorsiflexion, the Assessment of Preschool Children's Participation (APCP), and the Family Empowerment Scale (FES). Outcome evaluators were masked to group assignment and completed assessments at baseline, 6 months, and 9 months.
Ten children did not complete the full intervention, six in the child group and four in context group. GMFCS levels for children in the study were level I (n=37), level II (n=23), level III (n=21), level IV (n=21), and level V (n=26). There were no significant differences at baseline between the treatment groups for GMFCS level, parental education, or parental income. For the PEDI, there was no significant difference between the treatment groups, except for a small effect (p<0.03) on the Caregiver Assistance Mobility subscale between baseline and 9 months. The mean scores of both groups changed significantly on the Functional Skills Scales (p<0.001) and Caregiver Assistance Scales (p<0.02) of the PEDI after the 6-month intervention. There was no additional statistically significant change on the PEDI during the follow-up period from 6 to 9 months. A subgroup effect was found for age (p<0.001), with children younger than 3 years changing significantly more than older children. GMFCS level at baseline did not influence the amount of change on the PEDI scales. There were no significant differences between the treatment groups on the GMFM, range of motion measures, APCP or FES assessments. For the GMFM, there was a significant change over time from baseline to 6 months (p<0.001) and no significant change between 6 and 9 months. There was no adverse side effect as range of motion did not decrease in either group. Hip abduction increased significantly (p<0.01) at the 9-month assessment for both groups. For the APCP, significant changes for both treatment groups were found between baseline and 6 months for play intensity (p<0.04), physical activity intensity and diversity (p<0.001), and total score intensity (p<0.01).
This study shows that child- or context-focused therapy approaches are equally effective and that frequency of intervention may be a critical component of successful intervention. Further evaluation is required to identify the various `dose-response' relations of amount of treatment and changes in functional abilities.
We examine racial differences in health-related quality of life (HRQoL) among 2- and 3-year-olds born very low birthweight (VLBW, <1500g). The sample included 611 children (290 males and 321 females) from the Newborn Lung Project, a cohort of VLBW infants hospitalized in Wisconsin’s newborn intensive care units during 2003 to 2004. Of the 611 children, 14% (86/611) were black, non-Hispanic and 86% (525/611) were white, non-Hispanic and 4% (23/611) had cerebral palsy. HRQoL was measured using the Pediatric Quality of Life Inventory. Black children scored nearly 4 points lower (mean difference −3.6, 95% confidence interval [CI]: −6.9 to −0.3) on HRQoL than their white peers. Cerebral palsy is associated with lower HRQoL (mean difference −24.4, 95% CI: −29.3 to −19.5), especially among black children, but does not explain racial differences in HRQoL. Living in a neighborhood with lowest levels of female education is associated with lower HRQoL (mean difference −5.6, 95% CI: −9.2 to −2.1), but does not explain the racial difference in HRQoL.
Angelman syndrome is a neurogenetic disorder characterized by severe intellectual disability, absent speech, seizures, and outbursts of laughter. The aim of this study was to utilize diffusion tensor imaging (DTI) to examine alterations in white matter pathways in Angelman syndrome, with an emphasis on correlations with clinical severity.
DTI was used to examine the arcuate fasciculus (AF), uncinate fasciculus (UF), inferior longitudinal fasciculus (ILF), inferior fronto-occipital fasciculus (IFOF), and the corpus callosum (CC). We enrolled 14 children aged 8 to 17 years (mean age 10y 8mo; SD 2y 7mo) with Angelman syndrome (seven male; seven female) and 13 typically developing children, aged 8 to 17 years, for comparison (five male; eight female; mean age 12y; SD 2y 9mo). Individuals with Angelman syndrome were assessed using standardized measures of development, language, and behaviour.
The children with Angelman syndrome exhibited lower fractional anisotropy and increased radial diffusivity values than the comparison group for the AF, UF, ILF, and CC (p<0.006 corrected for multiple comparisons). They also had lower fractional anisotropy values for the IFOF and higher radial diffusivity values for the left IFOF (p<0.006). Additionally, children with Angelman syndrome had significantly higher apparent diffusion coefficient values in the AF, CC, ILF, and the left IFOF (p<0.006). Significant correlations were noted between DTI parameters and some of the clinical assessment outcomes (e.g. language, socialization, cognition) for three of the temporal pathways (AF, UF, ILF; p<0.05).
Changes in DTI parameters in individuals with Angelman syndrome suggest decreased/delayed myelination, decreased axonal density or diameter, or aberrant axonal organization. Our findings suggest a generalized white matter alteration throughout the brain in those with Angelman syndrome; however, only the alterations in temporal white matter pathways were associated with language and cognitive and social functioning.
Few data exist to aid the clinician in prognosis after paediatric intracerebral haemorrhages (ICHs). Recently, ICH volume as a per cent of total brain volume (TBV) was shown to help predict outcomes in children. Thus, we sought to develop a bedside method of TBV estimation using typical hospital imaging software, and to validate the ABC/2 method for children in order to determine ICH volume and aid prognosis.
The study group comprised 23 children and adolescents with non-traumatic, acute ICH who had undergone head computed tomography (CT) and who were available for analysis. The median age of participants, 14 males (61%) and nine females (39%), was 6 years (range 0–16y; mean 7.8y; SD 5.3y). Preterm infants born at less than 37 weeks’ gestation and term infants with pure intraventricular haemorrhages were excluded. Manual segmentation, which is the criterion standard for measurement of ICH volume and TBV, requires specialized software and is time-consuming. We therefore used the well-known ‘ABC/2 × slice thickness’ method to calculate ICH volume and TBV, thus allowing ICH size to be reported as a percentage of TBV regardless of the absolute size of ICH.
The estimated ICH volume was highly accurate compared with the criterion standard (R2=0.97 and R2=0.93; combined R2=0.96), as was the estimated TBV (R2=0.89 and R2=0.77; combined R2=0.83). The interrater reliability was high for both ICH volume and TBV, with an intraclass correlation coefficient (ICC) of 0.94 and 0.80, respectively. Therefore, using no specialized software, we accurately measured ICH volume as a percentage of TBV.
The ABC/2 × slice thickness method is a possible bedside tool for the clinician that can aid prognosis after paediatric ICH.
In children with bilateral spastic cerebral palsy (CP), periventricular leukomalacia (PVL) is commonly identified on magnetic resonance imaging. We characterized this white matter condition by examining callosal microstructure, interhemispheric inhibitory competence (IIC), and mirror movements.
We examined 7 children (age range 11y 9mo–17y 9mo, median age 15y 10mo, 4 females) with bilateral spastic CP/PVL (Gross Motor Function Classification System level I or II, Manual Ability Classification System level I) and 12 age-matched controls (age range 11y 7mo–17y 1mo, median age 15y 6mo, 7 females). Fractional anisotropy of the transcallosal motor fibers (TCMF) and the corticospinal tract (CST) of both sides were calculated. The parameters of IIC (transcranial magnetic stimulation) and mirror movements were measured using standardized clinical examination and a computer-based hand motor test.
Fractional anisotropy was lower in children with bilateral spastic CP/PVL regarding the TCMF, but not the left or right CST. Resting motor threshold was elevated in children with bilateral spastic CP/PVL whereas measures of IIC tended to be lower. Mirror movements were markedly elevated in bilateral spastic CP/PVL.
This study provides new information on different aspects of motor function in children with bilateral spastic CP/PVL. Decreased fractional anisotropy of TCMF is consistent with impairment of hand motor function in children with bilateral spastic CP/PVL. The previously overlooked microstructure of the TCMF may serve as a potential indicator for hand motor function in patients with bilateral spastic CP/PVL.
To examine the relation of axial and appendicular bone properties in ambulatory children with cerebral palsy (CP) to functional (Gross Motor Function Classification System [GMFCS]) level.
Quantitative computed tomography measurements were compared among 37 children with CP (12 children in GMFCS level I, five in level II, 18 in level III, two in level IV; five with hemiplegia, 23 with diplegia, two with triplegia, seven with quadriplegia; mean age 9y 4mo, SD 1y 6mo; 18 males, 19 females) and 37 children in a comparison group (same age and sex distributions). Linear regression was used to evaluate differences in volumetric cancellous bone density (vBMD) and geometric properties of the L3 vertebra and tibia, adjusting for height, weight, and sex as covariates.
The comparison group had larger vertebrae than the children with CP (p=0.02) owing to smaller vertebral size in GMFCS levels III and IV, but there was no difference in vertebral vBMD (p=0.49). In the tibia, bone volumetric density (p=0.09) and size (p=0.02) decreased with increasing GMFCS level. GMFCS level had a greater effect on bone size in females than in males (p<0.07).
Children with CP of all levels may have less bone in their tibias, whereas spine deficits differentially affect more involved children. Because even small bone deficits may manifest as osteoporosis later in life, it is important to study bone acquisition in all children with CP.
Rare diseases are always a real challenge. The first test is to remember the myriads of often obscure but frequently tell-tale clinical signs that lead to suspicion for a specific disease. The next is to recognize these signs in the clinic, something that is not easy unless you are looking for them. Then there is the difficulty of figuring out the appropriate diagnostic work-up. Getting samples to the right diagnostic centers often presents a logistical problem, and when the results return, how to manage the condition. Comprehensive care is particularly challenging, due to frequently hidden comorbidities. So how are these challenges to be handled for more than 3000 rare diseases?
Children with autism spectrum disorder (ASD) are reported to have decreased bone cortical thickness (BCT). Vitamin D plays an important physiological role in bone growth and development, so deficiency of vitamin D could contribute to decreased BCT. The goal of this study was to compare plasma 25(OH)D concentration in three groups of Caucasian males age 4 to 8 years old: (1) ASD and an unrestricted diet (n=40), (2) ASD and a casein-free diet (n=9), and (3) unaffected controls (n=40). No significant group differences were observed (p=0.4). However, a total of 54 (61%) of the children in the entire cohort had a plasma 25(OH)D concentration of less than 20ng/mL, similar to findings of low 25(OH)D concentrations in population-based studies. Children with ASD should be monitored for vitamin D deficiency.