A male and female with juvenile metachromatic leukodystrophy (MLD) with unusual manifestations are presented, each involving a novel arylsulfatase A gene mutation. One patient demonstrated acute intermittent encephalopathic episodes for 1 year after having received the diagnosis of MLD at the age of 6 years. The other patient presented at the age of 5 years with acute hemiparesis, which was diagnosed as acute disseminated encephalomyelitis and resolved in 3 weeks. After 2 years of remission he started to show progressive neurological deterioration. The episodic manifestations in both patients were associated with acute, resolving cerebral lesions on magnetic resonance imaging accompanying or preceding the classical demyelinating lesions of MLD. The diagnosis of MLD was based on arylsulfatase A enzyme activity levels and genetic analysis, and after the exclusion of neurological conditions such as encephalitis, vasculopathy, or mitochondrial disorders. The pathogenesis of this previously undescribed finding in MLD is unknown but might be related to a susceptibility of myelin to acute damage.

The case of a Yemeni girl with isolated peroxisomal acyl-CoA:dihydroxyacetonephosphate acyltransferase (DHAPAT) deficiency is reported. She had rhizomelic chondrodysplasia punctata, microcephaly, failure to thrive, delayed motor and mental development, and spastic quadriplegia. Deficient de novo plasmalogen synthesis in her fibroblasts as a result of low DHAPAT activity was found, while her very-long-chain fatty acid profile, phytanic acid concentration, alkyl-dihydroxyacetonephosphate synthase (alkyl-DHAP synthase) activity, and peroxisomal 3-ketoacyl-CoA thiolase protein were normal. A mutation in her DHAPAT complementary DNA resulted in the substitution of an arginine residue in the protein at position 211 by a histidine (R211H). Magnetic resonance imaging showed abnormal white matter signal in the centrum semiovale involving the arcuate fibers, while the corpus callosum was normal. DHAPAT and alkyl-DHAP synthase initiate the synthesis of plasmalogens, which are major constituents of myelin phospholipids. The reported girl's abnormal formation of myelin is probably related to the inadequacy of plasmalogen biosynthesis, which is likely to be due to deficient DHAPAT activity.

A 5-year old girl with cerebral palsy (CP), preterm birth, postnatal aortic thrombus, and cerebellar venous infarction who is homozygous for the thrombophilic factor-V Leiden (fVL) mutation is reported. The role of hereditary thrombophilic disorders in the development of perinatal vascular lesions such as aortic thrombi, renal-vein thrombosis, venous-sinus thrombosis, and cerebral infarction is unknown. This case report brings into question a potential association between fVL, perinatal vascular lesions, perinatal stroke, and CP.

Adeli suit treatment (AST) is a pertinent and timely topic for research. Many families and clinicians are interested in the outcomes of treatment using the Adeli suit, but the rehabilitation community does not have adequate scientific support for its use as a generally accepted treatment for cerebral palsy (CP). Very little research has been completed around non-traditional treatments such as AST. The study reported in this issue of DMCN by Bar-Haim et al. compared the use of AST and traditional neurodevelopment treatment (NDT) in children with CP.

The Kinaesthetic Sensitivity Test (KST) was used to measure the development of kinaesthetic acuity in adolescent boys. Thirty boys were tested longitudinally, at intervals of 6 months, between the ages of 11½ and 14 years. A second group of 20 boys was tested at the ages of 14 and 16½ years. The findings were compared with existing normative data on 5- to 12-year-old children and young adults, and they indicated improvement in kinaesthetic acuity with age. Although the age effect is statistically significant only in the older group, confidence intervals show that the rate of improvement in both groups is comparable to improvement between the ages of 5 and 12 years. The reliability of the test is rather poor. The conclusion is that kinaesthetic development continues throughout adolescence. Further, development is quite robust and detectable even with a fairly unreliable measurement instrument. However, individual assessments should be interpreted with caution.

A 5-year-old female presented with prolonged afebrile right-sided focal seizures, right brachio-facial paralysis, and dysarthria; consciousness was not altered. Fever appeared 20 hours after onset of neurological symptoms. At admission (day 1) cerebral computerized tomography and cerebrospinal fluid (CSF) analyses were normal including undetectable alpha-interferon (α-IFN) and negative herpes simplex virus (HSV) polymerase chain reaction (PCR). Acyclovir was started at a dosage of 60mg/kg/day for 21 days and neurological symptoms improved. Cerebral magnetic resonance imaging (MRI) showed lesions in the left thalamus and left parietal lobe. On day 8, CSF contained an elevated leukocyte count with a predominance of lymphocytes, but α-IFN and HSV DNA were still undetectable. Delayed intrathecal synthesis of specific anti-HSV antibodies was found on day 26 and confirmed herpes simplex encephalitis (HSE) diagnosis. Twenty months after this episode, the patient presented with a febrile meningeal syndrome. PCR detected HSV DNA in CSF and cerebral imaging showed a new left temporal lesion. At relapse onset, intrathecal synthesis of specific anti-HSV antibodies had disappeared. Acyclovir was started at a dosage of 60mg/kg/day for 21 days and neurological status improved. At discharge, neurological examination showed right hemiparesis and bucco-facial dyspraxia. Diagnostic problems of HSE diagnosis in children are highlighted. It is suggested that the premature disappearance of intrathecal synthesis of a specific anti-HSV antibody might play a permissive role in the resurgence of cerebral viral replication.

Ultrasound images were obtained of the medial gastrocnemius at different ankle joint positions with the knee extended. Fascicle length and deep fascicle angle were measured in five normally developing adults (mean age 33 years, age range 24 to 36 years) and in five normally developing children (mean age 7.8 years, age range 7 to 11 years), and in seven children with spastic diplegia (mean age 10 years, age range 6 to 13 years). These architectural variables were similar in the groups of normally developing adults and children. Importantly, no statistical difference could be found between the normally developing children and those with diplegia for fascicle length. Deep fascicle angles were reduced significantly in the clinical group at a particular ankle joint angle but not at the resting angles. The difference in deep fascicle angles is explained as a function of resting muscle length and is not attributed any clinical importance. Our results do not explain the structural origin of muscle contracture explicitly. However, they do indicate that most of the fixed shortness in the medial gastrocnemii of ambulant children with spastic diplegia is not due to reduced muscle fascicle length. We suggest that muscle contracture may be better explained in terms of shortness of the aponeuroses of pennate muscles, such as the medial gastrocnemius, through reduced muscle fascicle diameter.

The purpose of this study, through a retrospective epidemiological survey carried out over three geographical areas in France, was to characterize the aetiological factors involved in severe mental retardation (SMR) within a geographically defined population of children with disabilities aged between 7 and 16 years. The inclusion criteria for SMR (IQ<50) were met by 1150 children born between 1976 and 1985. Of these children, aetiology was known in 25%, suspected (or unclear) in 26%, and unknown in 49%. These rates of known and suspected aetiology varied between the groups of children with CP and those without CP. An analysis of factors associated with SMR was undertaken among the 144 subjects with SMR, of suspected or unknown aetiology, who had been referred to a neonatal care unit with or without intensive care (NCU) during their neonatal period. These subjects with SMR were compared with 864 children without SMR (control children) who were also referred to an NCU during their neonatal period. The main specific associated factors were a prolonged intubation of more than 24 hours, a very low birthweight (<1500 g) for children with an associated clinical feature of CP, and the presence of isolated neonatal fits and a time of transfer to the NCU of more than 4 hours after birth for children without an associated clinical feature of CP. Although common associated factors were encountered in the children with SMR with CP and the children with SMR without CP, the results of this study suggest differences in the underlying pathogenic factors.

Among key points in making progress and succeeding with a therapeutic programme for children with disabilities is parental compliance with the regime for their child. The purpose of this study was to evaluate factors influencing compliance with home therapy in the Jewish and Bedouin populations. Data were collected by structured questionnaires. A total of 193 families participated (84% response rate) with children who ranged in age from 6 months to 6 years (mean age at first visit to the centre was 9.5 years in Jews and 16.1 years in Bedouin). Compliance was significantly lower among the Bedouin. Multivariate regression analysis showed that the strongest contributory factor in lack of compliance was being Bedouin. The second factor was intensity of questioning destiny, indicating that parents with these feelings may be less likely to comply with therapeutic regimes. Other factors which were associated with compliance were parents' education and socioeconomic status: lower levels on these dimensions corresponded with lower parental compliance. These results were illuminated by a trial intervention programme for Bedouin families which involved telephone contact, translation facilities, and detailed explanations during visits to the centre. Intervention increased the compliance rate of the Bedouin appointments with specialists to 76% (91 of 120 appointments) thereby reaching similar levels to those of the Jewish group. These preliminary results indicate that the strong association between non-compliance and being Bedouin may be due to factors of communication, and that the Bedouin are receptive to therapeutic interventions when communicated in their own language.

Somatosensory evoked potentials (SSEPs) are a very sensitive measure of the functional integrity of the neuroaxis, including peripheral and central structures. When used in diagnostic mode they can provide additional information regarding the probable areas of dysfunction. SSEPs were recorded from 44 children (64 feet with congenital talipes equinovarus, CTEV), between the ages of 2 to 15 years, who had structural CTEV deformity previously treated by surgery, with no clinical evidence of neurological deficit. SSEPs were elicited after sequential and bilateral stimulation (0.1ms/5Hz/10 to 20mA) of the posterior tibial nerve and the common peroneal nerve and were recorded cortically (P40). In half the children, additional recordings were conducted at the knee (N5), the first lumbar spinous process (N14), and the seventh cervical spinous process (N20). Eighteen children had abnormal responses, four children had non-reproducible responses, and 22 children had normal responses. Analysis of the data at different levels of the nervous system showed that eight children had abnormality at the spinal level. The surgical outcome was influenced by the neurological abnormality, with an excellent or good outcome in 34 of 36 feet with normal neurology and 19 of 28 feet where a deficit was present (p<0.05). These findings support the neurological theory as an etiological factor in CTEV deformity.

This study aimed to assess the visuospatial abilities of five children with Williams syndrome (four males aged 9 years 3 months, 7 years 11 months, 8 years 1 month, and 10 years 8 months respectively, and one female aged 6 years 3 months). First, the children's visuospatial abilities were examined by asking them to copy a figure. Second, their cognitive processing abilities were assessed using the Japanese Kaufman Assessment Battery for Children. This test was used because it is an objective one, standardized in Japan, and is a measure of fluid ability including spatial localization. Participants scored significantly low on the spatial memory subtest indicating that there was a deficit in spatial localization. Children's performance in line copying tasks improved when the dots were in colour. Results suggest a deficit in the dorsal stream of visual cognition, with a relatively preserved ventral stream.

Acquired epileptic aphasia (AEA, or Landau–Kleffner syndrome) is a unique condition in which children can lose oral language (OL) comprehension and expression for a prolonged period. These children can benefit from visual forms of language, mainly sign language (SL), but the quality of SL has never been analyzed. The case is reported here of a boy with AEA who lost speech comprehension and expression from 3 years 6 months to 7 years and was educated in SL from the age of 6 years. His SL was evaluated at the age of 13 years and 6 months and compared with a control child with congenital sensorineural deafness. It was found that: (1) our patient achieved the same proficiency in SL as the control child with deafness; (2) SL learning did not compete with, but perhaps even hastened, the recovery of OL. Intact ability to learn a new linguistic code such as SL suggests that higher-order language areas were preserved and received input from a separate visual route, as shown by neuropsychological and functional imaging research in deaf and hearing signers.

Ocular motor apraxia (OMA), a disorder of saccadic initiation, may be congenital or acquired. While the acquired form is frequently associated with significant neuropathology, the congenital form is often regarded as relatively benign. Many children with congenital OMA who were observed clinically have shown neurodevelopmental disturbance over time. A retrospective review was taken of 34 consecutive patients (22 males and 12 females), seen over a 20-year period, to evaluate the frequency and type of associated neurodevelopmental problems. Age at presentation ranged from 8 weeks to 14 years, with a mean age of 10 years. Of 29 children with congenital OMA, 15 had imaging evidence of structural central nervous system abnormalities (with cerebellar hypoplasia the most frequent abnormality detected). Eleven of the 14 patients with no structural abnormality showed abnormal neurodevelopment. This study suggests that congenital OMA is not a benign diagnosis, even in the absence of overt neurological disturbance at the time of presentation.

Direct measurement of energy expended by spasticity in children with severe spastic quadriparesis is difficult. Insertion of an intrathecal baclofen pump in a 13-year-old boy with severe spasticity and profound mental retardation resulted in an estimated 30 to 40% decrease in his spasticity. As he had been on a carefully calculated ketogenic diet and fed by gastrostomy, his precise caloric intake was known. Decrease in spasticity, on the same caloric intake, led to marked weight gain. Reduction of 100 calories intake resulted in new weight stability. It was possible therefore, to estimate indirectly energy used by his spasticity. This 100 calories, representing 34% of calories above his resting energy requirement, corresponded to an independently estimated 30 to 40% of caloric expenditure of his spasticity. It was concluded that when calculation of calories is critical, energy utilization by spasticity must be taken into consideration.

An 8-year-old female presented with a distinct clinical course characterized by an acute self-limiting chorea-encephalopathy with cerebrospinal fluid (CSF)-specific oligoclonal bands. During the clinical course, genomic human parvovirus B19 DNA was detected in her serum and CSF. It was concluded that this patient represents the first published case of childhood chorea-encephalopathy associated with, and probably caused by, human parvovirus B19 infection.

To determine the effect of intravenous porcine secretin on autistic behaviours in children aged 2 to 7 years, the effects of secretin on (1) performance on a standardized language measure, and (2) autistic behaviours, as rated by parents and child development professionals was examined. Employing a randomized, double-blind, placebo-controlled design, 95 participants were assigned to one of two groups and administered a single dose of either secretin or placebo. A follow-up assessment was conducted 3 weeks after the injection. No significant differences in language or autistic behaviour measures were observed at the 3-week follow-up between the groups. Also, there was no significant difference in the proportion of individuals who improved by [ges ] 6 points on the language measure at follow-up. This study showed no significant effects of secretin on children with autism. Our results are consistent with a systematic review of randomized controlled trials evaluating the effect of secretin in children with autism.

Data are presented on 157 newborn infants followed sequentially in a randomized home-based nursing-intervention trial for drug-exposed infants with follow up at 3 (N=118), 6 (N=124), and 12 months (N=77). The objectives of this study were to describe the longitudinal neurodevelopmental status of a cohort of children with intrauterine exposure to illicit drugs during their gestation, characterize the evolution of early tone abnormalities in a polydrug-exposed cohort, and determine whether neuromotor outcome is associated with drug-exposure patterns. For analysis, infants were grouped based on maternal drug-use pattern and the presence of drug metabolites in the neonatal drug screen. The sequential neuromotor examination was used at each age to define the neuromotor status of six domains and define categorical classifications as either normal, suspect, or abnormal. Multiple patterns of neuromotor abnormalities were observed during the neonatal period; most resolved over time. Axial hypotonia was a prominent finding in the neonatal period; however, it was infrequent in abnormal examinations at 12 months. Increased lower-extremity tone was a less frequent finding during the neonatal period. Infants whose neonatal urine drug screen was positive for both cocaine and opiates, were more likely than infants with negative urine drug screens, cocaine only, or opiate only drug screen results to have abnormal neuromotor examinations; while positive maternal drug screens for concurrent cocaine and opiate use were associated with peripheral hypertonia. Persistence of increased leg-extensor tone was found in 67% of the abnormal examinations at 12 months. Acquisition of rolling and walking was delayed in the drug-exposed cohort.

All children who present in a convulsion, including convulsive status epilepticus, to the accident and emergency department over a 12-month period and who required treatment, were reviewed retrospectively to identify the effectiveness and safety of a specific treatment protocol. This protocol recommends the initial use of one, or if necessary, two doses of rectal or intravenous diazepam (0.4mg/kg) followed by the simultaneous administration of phenytoin (18mg/kg) and rectal paraldehyde (0.4mL/kg), with instructions for maximum doses and timings of administration. Eighty-one evaluable children (52 male) were audited. The mean age of the study population was 4.1 (range 0.1 to 14.9) years. Overall, the presenting convulsion was successfully terminated in 76 children (94%) within the accident and emergency department. In 69 children (85% of the entire study population) this was after a single dose of diazepam (rectal in 41 and intravenous in 28). In only an additional two children did the presenting convulsion stop after a second dose of diazepam. In five of the 10 children (50%) who received paraldehyde and phenytoin as a combination, the convulsion stopped. Nine patients (11%) required admission to the intensive-care unit, five because of persisting convulsive activity, and four because of respiratory depression. The results of this retrospective audit suggest that the current treatment protocol appears to be effective and relatively safe in treating acute convulsions, including convulsive status epilepticus. The audit is to be repeated prospectively to either confirm or refute these findings before recommending any changes to the protocol.

Velocardiofacial syndrome is identified by a submicroscopic deletion of chromosome 22q.11 (del22q.11). This study presents data on the early motor development and behaviour of 11 children (8 males, 3 females) with del22q.11 (mean age 41mo, SD 9.7mo) with a congenital heart defect. To control for the impact of the congenital heart defect, a control group of 19 children (15 males, 4 females; mean age 46mo, SD 9mo) with the same types of congenital heart defects but without del22q.11 was selected. Motor development in both groups was measured with the Peabody Developmental Motor Scales-2. Behaviour was assessed with the Child Behaviour Checklist. Children with del22q.11 scored significantly lower (p<0.05) on motor performance than the children of the control group. Most deficient motor skills were found for the subtests Locomotion and Stationary. On the behaviour questionnaire, a statistically significant (p<0.05) difference between the two groups was found only for the subscale Withdrawn. These data reveal a significant motor delay in many young children with del22q.11, which is not caused by the presence of a congenital heart defect or by behavioural features.

The aim of this study was to investigate psychosocial, cognitive, and motor functioning in patients clinically suspected of Sotos syndrome and to examine differences between patients with deletions or mutations of the gene encoding nuclear SET domain-containing protein 1 (NSD1; the major cause of the syndrome) and those without such alterations. Twenty-nine participants (21 males, 8 females) clinically suspected of Sotos syndrome (mean age 11y 10mo [SD 10y 11mo], range 1y 10mo–48y 5mo) were divided into an NSD1 mutation group (n=12; 8 males, 4 females) and an NSD1 non-mutation group (n=17; 13 males, 4 females). Intelligence, behaviour problems, attention-deficit–hyperactivity disorder (ADHD) symptoms, temperament, adaptive behaviour, and motor functioning were assessed with an extensive test battery. Scores were compared with those of control groups, and scores of the two subgroups were compared with each other. The mean IQ in the 21 individuals tested was 76 (SD 16; range 47–105). High rates of behaviour problems were found and patients lagged 1y 7mo to 2y 7mo behind in aspects of adaptive behaviour. In comparison with a control group of patients with a learning disability, motor functioning was better. NSD1 mutation compared with NSD1 non-mutation patients showed easier temperament, and fewer NSD1 mutation patients scored in the clinical range for ‘total behaviour problems’ (3/11 vs 13/17), ‘internalizing behaviour’ (2/11 vs 11/17), and ADHD (0/9 vs 4/15).