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Each year Developmental Medicine and Child Neurology (DMCN) invites the President Elect of the American Academy for Cerebral Palsy and Developmental Medicine (AAPCDM) to compose a guest editorial. As we mark the 60th anniversary of the Academy, I welcome the opportunity to make a few observations on the emergence of the internet as a medium that, within the space of two decades, has had an increasing influence upon both medical research and its dissemination throughout the world. Although the Academy's founding fathers certainly recognized that communication was the key to future progress, it is unlikely that they could have imagined what was ahead in terms of instantaneous information exchange or how that capability would promote collaboration at great distances, speed up the decoding of the human genome, and empower patients with information that previously had largely been the province of academia. This September, portions of our annual meeting will be webcast from Boston to 10 locations in four different countries around the world. Individuals who cannot attend the meeting in person will have an opportunity to view the lectures, and then, in special sessions, to engage in real-time exchanges with many of the presenters. In addition, the AACPDM now presents a monthly 1-hour webcast for entitled members concentrating on timely subjects by world-renowned authorities.
In recent years, bisphosphonates, primarily intravenous (iv) pamidronate, have become very widely used in children with severe osteogenesis imperfecta (OI). This has occurred without the well-controlled clinical trials usually required before a medication becomes ‘standard care’. Without placebo-controlled trials it is difficult to define precisely the risks and the benefits, but in children with very severe OI and numerous fractures the risk/benefit ratio is so clearly favorable that widespread use of pamidronate in this situation appears appropriate.
The aim of this study was to test the efficacy of low doses of pamidronate in increasing bone mineral density (BMD) in non-ambulatory children and adolescents with cerebral palsy (CP). Twenty-three non-ambulatory children and adolescents (12 females, 11 males; mean age 10y [SD 5y], range 4y 1mo–17y 11mo) with severe spastic quadriplegic CP and low BMD were recruited from a multidisciplinary clinic. Severity of CP was graded at Level IV (n=10) and Level V (n=13) using the Gross Motor Function Classification System. Patients received intravenous pamidronate (4.12mg/kg/y, maximum 45mg/d) every 4 months. Lumbar spine and femoral neck BMD were measured at baseline and after 4 and 12 months. Twelve months after the first dose of pamidronate there was a significant increase in lumbar spine and femoral neck BMD (p<0.01 for both sites) and z scores compared with baseline values (p<0.01 for both sites). Mean BMD z scores increased 1.6 points for femoral neck and 1.9 points for lumbar spine after 12 months of pamidronate treatment. Serum intact parathyroid hormone increased significantly and cross-linked N-teleopeptide of type I collagen decreased significantly at 12 months. No significant side effect was noted. Low doses of pamidronate are well tolerated and significantly increase BMD in non-ambulatory children and adolescents with CP.
Using a semi-structured questionnaire, this descriptive study examined perceptions of feeding and adherence to feeding recommendations for caregivers (26 females; mean age 32y 7mo [SD 9.4y], range 20–59y) of children with cerebral palsy (CP) and a gastrostomy tube (GT). Children in the study (15 females, 11 males; mean age 4y 8mo [SD 3y 11mo], range 8mo–16y) had had a GT in place for at least 1 month and been assessed at Level II (n=2), Level III (n=2), Level IV (n=5), and Level V (n=17) of the Gross Motor Function Classification System. A negative response was reported by 18 caregivers when the GT was recommended; however, 21 caregivers reported improvement in the children following placement. All children received formula through the GT that was adequate for complete nutrition, yet 14 caregivers gave other foods through the GT (e.g. juice, cereal, soup, or table food). Of the 17 children receiving oral feedings, meals were an unpleasant experience for over half. Of the remaining nine children, in spite of a strict nil by mouth recommendation by physicians, five continued to receive some oral feedings. Generally, caregivers perceived GT feeding as ‘unnatural’. Understanding these perceptions will help clinicians to develop effective, family-centered, patient-appropriate intervention and adherence strategies for GT-fed children with CP.
Motor performance and movement quality were quantitatively examined (Zurich Neuromotor Assessment: timed motor performances and associated movements) in 87 prospectively enrolled very-low-birthweight (VLBW; <1250g) children (38 males, 49 females; mean birthweight 1016.2g [SD 141.5]:, range 720–1240g; mean gestational age 28.7wks [SD 2], range 25.7–33.4wks) at 6 years of age. All motor tasks were below the reference population: pure motor (median z-score) –0.46; adaptive fine motor (pegboard) –0.99; adaptive gross motor –0.88; static balance –0.48; and associated movements –1.90. All tasks correlated with the degree of neurological abnormalities (p[les ]0.004). VLBW children with no neurological abnormality also performed below the 10th centile and associated movements occurred more frequently than in the reference population (odds ratio 18, 95% confidence interval 6.7–47.9). Severity of periventricular leukomalacia and intraventricular haemorrhage assessed by ultrasound was associated with adaptive fine and gross motor tasks. We conclude that speed of motor performance and movement quality in particular were substantially impaired in VLBW children and are related to the degree of neurological abnormalities and neonatal cerebral injury.
Upper limb impairment can affect the ability to perform and participate in activities of daily living. The level of activity and participation limitation in the home environment for children with hemiplegic cerebral palsy (CP) is poorly understood. A greater understanding of these limitations could be used to provide targeted and appropriate intervention programmes. Level of activity and participation limitation were investigated, with the use of the Assessment of Motor and Process Skills (AMPS) in a representative sample of 54 South Australian children (31 males, 23 females) with hemiplegic CP, aged 3 to 12 years (mean age 7y 4mo [SD 2y 5mo]). Two AMPS tasks that were familiar to the child were performed in the home under the supervision of a trained occupational therapist. Findings suggested that younger children (3–8y) performed significantly better than older children (9–12y) for motor skill ability (0.46 vs 0.09, p=0.041) but not for process skill ability (–0.25 vs –0.28, p=0.885). Functional performance for the sample was below that of age-matched normative data. Motor performance in activities of daily living as detected by the AMPS seemed to worsen with age in children with hemiplegic CP. Further investigation into what can influence this outcome is required.
This study compared the passive stiffness of wrist flexors and the strength of wrist flexors and extensors in three different wrist positions (30° of flexion, neutral, and 30° of extension) between children with cerebral palsy (CP) and typically developing (TD) comparison children. It also examined associations between these characteristics and manual function in children with CP. Eleven children with spastic hemiplegic CP (six females, five males; mean age 8y 5mo [SD 1y 8mo], range 6–11y) and 11 TD children, matched for age and sex, took part in this study. Passive stiffness of muscles was measured as the torque/angle relation during passive motion. Isometric strength tests were performed and the time needed to complete three tasks based on the Jebsen–Taylor Hand Function Test was recorded. Flexor stiffness was higher in the group with CP. Strength of flexors and extensors in the group with CP was lower with the wrist extended. No difference among test positions was found in the TD group. Moderate correlations were observed between manual function and variables related to strength and stiffness of wrist muscles in the group with CP. Children with CP showed muscle alterations coherent with the use of the wrist in flexion. Intervention on these characteristics could have a positive impact on manual function.
The present study investigated the reliability of self-reported rating of Gross Motor Function Classification System (GMFCS) levels compared with professional rating, and changes in gross motor function over time, in adults with cerebral palsy. Twenty-nine females and 33 males aged between 18 years 5 months and 62 years 11 months (mean age 34y 7mo [SD 10y 6mo]) participated in the study. Participants rated their current gross motor function using the GMFCS and reported their judgement of their gross motor function at age 10 to 12 years. The project leader, a physical therapist, also classified participants' current GMFCS levels and conducted a chart review on all accessible medical records of participants' gross motor function when they were 10 to 12 years old, rating the GMFCS level accordingly. Intraclass correlation coefficients (ICC) between self-reported and professional ratings showed excellent agreement (ICC=0.93–0.95, 95% confidence interval [CI] 0.89–0.97). More than half the participants experienced a stable gross motor function from the age of 10 to 12 years to the present. Those at GMFCS Levels II and III at the age of 10 to 12 years (according to the professional rating) had significant change for the worse in gross motor function over time, with odds ratios of 9.30 (95% CI 1.2–73.0, p=0.03) and 7.00 (95% CI 1.1–43.0, p=0.04) respectively. Interview data on circumstances regarding changes in gross motor function since childhood are also reported. Changes in GMFCS level were mostly associated with physical or social environmental factors.
In the development of a new diagnostic motor performance test to spare more children from painful muscle biopsy, seven functional items were used to measure muscle strength and muscle endurance in a prospective study on new patients. Over a 2-year period, 22 patients (12 males, 10 females; mean age 8y 1mo [SD 2y 6mo], range 4–11y) were recruited for the study. They had all been referred with suspected myopathy. The motor performance test was administered before muscle biopsy. Validity of the seven items was assessed using logistic regression analysis and receiver operating characteristic (ROC) analysis. Two items were withdrawn from the test because they were not suitable for children aged 4 to 5 years. The five remaining items were: Heels, Circuit, Stairs, Jump, and Gowers. A full logistic regression model including these five items was fitted to the total population of 90 patients suspected of having myopathy (from this study and our previous study) to make the best prediction of whether myopathy was present. The ROC area under the curve of the diagnostic prediction model was 0.92 (95% confidence interval [CI] 0.87–0.98) and 0.89 (95% CI 0.87–0.92) after bootstrap correction. This indicated the high diagnostic power that can be expected for future, similar patients. This non-invasive and child-friendly motor performance test can improve diagnostic procedure and, therefore, spare more children from unnecessary muscle biopsy.
In children with nocturnal enuresis, a higher rate of minor neurological dysfunction has been found. The aim of this study was to assess timed performance (a measure of motor performance speed) and associated movements using a standardized and reliable instrument. The motor function of 37 children with nocturnal enuresis (27 males, 10 females; mean age 10y 7mo [SD 1y 10mo]; age range 8y–14y 8mo) and 40 comparison children without enuresis (17 males, 23 females; mean age 10y 7mo [SD 1y 6mo]; age range 8y–14y 8mo) was assessed using the Zurich Neuromotor Assessment. Children with nocturnal enuresis showed a slower motor performance than comparison children, particularly for repetitive hand and finger movements. This study provides evidence for a maturational deficit in motor performance in children with nocturnal enuresis. In addition to a maturational deficit of the brainstem, it is proposed that there is a possible maturational deficit of the motor cortex circuitry and related cortical areas in children with nocturnal enuresis.
There has been little exploration of major biologic regulators of cerebral development in autism. We measured insulin-like growth factors (IGF) -1 and -2 from cerebrospinal fluid (CSF) by radio immunoassay in 25 children with autism (median age 5y 5mo; range 1y 11mo–15y 10mo; 20 males, 5 females), and in 16 age-matched comparison children without disability (median age 7y 4mo; range 1y 1mo–15y 2mo; eight males, eight females). IGF-1 and -2 concentrations were further correlated with age of patients and head size. CSF IGF-1 concentration was significantly lower in patients with autism than in the comparison group. The CSF concentrations of children with autism under 5 years of age were significantly lower than their age-matched comparisons. The head circumferences correlated with CSF IGF-1 in children with autism but no such correlation was found in the comparison group. There was no difference between the two groups in CSF IGF-2 concentrations. No patients with autism had macrocephaly. We conclude that low concentrations of CSF IGF-1 at an early age might be linked with the pathogenesis in autism because IGF-1 is important for the survival of Purkinje cells of the cerebellum. The head growth might be explained by the actions of IGF-1 and -2 reflected in CSF concentrations.
Pyruvate dehydrogenase (PDH) deficiency is a major cause of neurological dysfunction and lactic acidosis in infancy and early childhood. The great majority of cases (>80%) result from mutations in the X-linked gene for the E1α subunit of the complex (PDHA1). Mutations in the genes for the other subunits have all been described, but only dihydrolipoamide dehydrogenase (E3) and E3 binding protein (E3BP) defects contribute significantly to the total number of patients with PDH deficiency. Although previously considered rare, with only 13 reported cases, we have found that mutations in PDX1, the gene for the E3 binding protein, are in fact relatively common. Clinical, biochemical, and genetic features of six new patients (four males, two females; age range 15mo–6y) with mutations in this gene are compared with previously reported cases. All patients with E3BP deficiency identified to date have mutations which completely prevent synthesis of the protein product. However, they are generally less severely affected than patients with PDHA1 mutations, although there is considerable overlap in clinical and neuroradiological features.
The aim of this study was to investigate how parents cope with and care for a child with Dravet syndrome, a severe myoclonic epilepsy with three distinct stages. Twenty-four parents of children with Dravet syndrome participated in a semi-structured interview and 17 completed the Impact of Childhood Neurologic Disability Scale (ICND) questionnaire. Children included 11 males and 13 females aged 2 to 24 years (mean age 10y 2mo [SD 5y 8mo]). Stage 1 of the syndrome was generally very difficult. Uncertainty about the diagnosis was the primary cause of stress. Seizure control was worst during this time. The primary concern in Stage 2 remained seizure control but developmental, behavioral, and sleep issues also emerged. Negative effects were noted in parents' relationships with others. Stage 3 brought better seizure control but decreased cognitive level, increased behavioral problems, and increasing social isolation for parents. Respite and relief care were hard to obtain at each stage. ICND scores mirrored the findings of the interviews. The three stages of Dravet syndrome present serious challenges for parents. Seizures are persistent and severe but developmental, behavioral, and sleep issues add to the stress. In the absence of successful medical treatment for Dravet syndrome, further attention needs to be paid to helping families cope with the disorder.
Landau–Kleffner syndrome (LKS) is an acquired childhood aphasia associated with paroxysmal bitemporal electroencephalogram (EEG) abnormalities and, sometimes, clinical seizures. We report the case of a female aged 5 years 6 months who presented clinically with apparent hearing loss, deterioration in speech, and seizure activity over 12 days. The female had previous detailed speech/language assessments at 3 to 4 years of age due to articulation delay. LKS was diagnosed on EEG with bitemporal spike and wave activity during sleep. The patient was treated with high dose prednisolone 3mg/kg/day, intensive speech/language therapy, and followed a modified educational program. We recorded a marked regression in receptive and expressive language skills, as well as her speech, language, and cognitive profiles before and during treatment with prednisolone, during an 18-month follow-up period. The patient demonstrated an excellent clinical response highlighting the importance of a multidisciplinary approach to management of LKS.
It has been suggested that Chlamydia pneumoniae (C. pneumoniae) is involved in the pathogenesis of diverse diseases of the central nervous system (CNS), including multiple sclerosis. We report the case of a 12-year-old male with isolated recurrent optic neuritis and an associated CNS infection with C. pneumoniae. The patient presented with three attacks of optic neuritis within 5 months. A positive polymerase chain reaction for C. pneumoniae in the cerebrospinal fluid led to the diagnosis of a CNS infection with C. pneumoniae. After treatment with the antibiotic rifampicin, he experienced no further attacks during the follow-up period of 6 years. These findings suggest the possibility of a C. pneumoniae infection as a contributing factor or even causative event for the development of optic neuritis.
Neurophysiological studies of sleep have increasingly focused on underlying dynamic processes. This would appear particularly relevant to the developmental aspects of sleep. Involvement of sleep-dependent mechanisms in emotional processing, as well as perceptual-sensory, perceptual-motor, and cognitive learning, mostly studied in adults, may play major roles in development. Rapid eye movement (REM) sleep, which is generated by complex neuronal interactions within the pontine reticular formation, and non-REM sleep, which arises from activities in the thalamocortical network, are specifically implicated in different aspects of long-term memory systems. They evolve from previous physiological and behavioural states which can be traced back to the fetal period. Further studies are needed to clearly identify functions reflected by hallmarks of sleep stages, such as spindles and K complexes. A better understanding of the maturational aspects of sleep should provide important insights into physiological development. Assessment approaches taking dynamic characteristics of sleep into account may contribute to the design of better targeted management of sleep-related problems in neurodevelopmental conditions.
Review of the definition of cerebral palsy (CP) has focused on disorders of movement and posture development that cause activity limitations. Recent research provides new insights into CP, showing that activity limitation in individuals with hemiplegic CP is not exclusively caused by disorders related to movement execution, but is also related to the planning of movements. In this review article, converging evidence is presented suggesting that, in addition to movement execution impairments, impairments in movement planning may also limit the performance of activities of daily living. Evidence from studies of fingertip-force planning and anticipatory planning in object manipulation tasks is discussed.
During a discussion at the autumn 2005 DMCN Editorial Board meeting, I mentioned that prior to becoming a doctor I worked as an engineer analyzing nuclear weapons' testing data. After the meeting, Dr Jean-Pierre Lin suggested, that in the current world climate, I write an editorial on how I intellectually and morally underwent a metamorphosis from an expert in high atmospheric nuclear physics to a specialist surgeon in the care of children with disabilities. I feigned interest but brushed it off in my own mind as quickly as possible. I have always had, and continue to have, the greatest respect for the men and women who wear the military and civilian uniforms of our nations. Furthermore, my work was done more than 25 years' ago and is now, no doubt, relegated to obscure government reports and possibly doctoral theses.