Small biparietal diameter and head circumference are part of the phenotype instead of independent prognostic markers in fetuses with spinal dysraphism.

OBJECTIVE: The aim of this retrospective study was to assess the fetal biparietal diameter (BPD) and head circumference (HC) in the second trimester of pregnancy in fetuses with open spinal dysraphism. METHODS: BPD and HC were measured at 16-26 weeks in 74 fetuses with open spinal dysraphism and compared with reference values. RESULTS: BPD was smaller in fetuses with open spinal dysraphism. Of all cases with open spinal dysraphism, 62.2% had a BPD <3rd percentile and 79.7% had a BPD <10th percentile. Of all patients, 54.1% had an HC <3rd percentile and 74.3% had an HC <10th percentile. CONCLUSION: Almost all fetuses with open neural tube defects have a smaller BPD and HC at 16-26 weeks compared with reference values, which implicates that this is part of the phenotype of children with open spinal dysraphism instead of an independent prognostic marker for a poor cognitive outcome.

Clinical practice: swallowing problems in cerebral palsy.

Cerebral palsy (CP) is the most common physical disability in early childhood. The worldwide prevalence of CP is approximately 2-2.5 per 1,000 live births. It has been clinically defined as a group of motor, cognitive, and perceptive impairments secondary to a non-progressive defect or lesion of the developing brain. Children with CP can have swallowing problems with severe drooling as one of the consequences. Malnutrition and recurrent aspiration pneumonia can increase the risk of morbidity and mortality. Early attention should be given to dysphagia and excessive drooling and their substantial contribution to the burden of a child with CP and his/her family. This review displays the important functional and anatomical issues related to swallowing problems in children with CP based on relevant literature and expert opinion. Furthermore, based on our experience, we describe a plan for approach of investigation and treatment of swallowing problems in cerebral palsy.

Essential features of Chiari II malformation in MR imaging: an interobserver reliability study--part 1.

PURPOSE: Brain MR imaging is essential in the assessment of Chiari II malformation in clinical and research settings concerning spina bifida. However, the interpretation of morphological features of the malformation on MR images may not always be straightforward. In an attempt to select those features that unambiguously characterize the Chiari II malformation, we investigated the interobserver reliability of all its well-known MR features. METHODS: Brain MR images of 79 children [26 presumed to have Chiari II malformation, 36 presumed to have no cerebral abnormalities, and 17 children in whom some Chiari II malformation features might be present; mean age 10.6 (SD 3.2; range, 6-16) years] were blindly and independently reviewed by three observers. They rated 33 morphological features of the Chiari II malformation as present, absent, or indefinable in three planes (sagittal, axial, and coronal). The interobserver reliability was assessed using κ statistics. RESULTS: Twenty-three of the features studied turned out to be unreliable, whereas the interobserver agreement was almost perfect (κ value > 0.8) for nine features (eight in the sagittal plane and one in the axial plane, but none in the coronal plane). CONCLUSIONS: This study presents essential features of the Chiari II malformation on MR images by ruling out the unreliable features. Using these features may improve the assessment of Chiari II malformation in clinical and research settings.

Interobserver reliability and diagnostic performance of Chiari II malformation measures in MR imaging--part 2.

PURPOSE: Brain MR imaging is essential in the assessment of Chiari II malformation in clinical and research settings concerning spina bifida. However, the interpretation of MR images of the malformation is not always straightforward. Morphometric analyses of the extent of Chiari II malformation may improve the assessment. In an attempt to select appropriate morphometric measures for this purpose, we investigated the interobserver reliability and diagnostic performance of several morphometric measures of Chiari II malformation on MR images. METHODS: Brain MR images of 79 children [26 with open spinal dysraphism, 17 with closed spinal dysraphism, and 36 without spinal dysraphism; mean age 10.6 (SD 3.2; range, 6-16) years] were evaluated. All children had been assessed for Chiari II malformation (defined as cerebellar herniation in combination with open spinal dysraphism; n = 23). Three observers blindly and independently reviewed the MR images for 21 measures of the cerebellum, brainstem, and posterior fossa in three planes. The interobserver reliability was assessed by an agreement index (AI = 1 - RRE) and the diagnostic performance by receiver operating characteristic analyses. RESULTS: Reliability was good for most measures, except for the degree of herniation of the vermis and tonsil. Most values differed statistically significantly between children with and without Chiari II malformation. The measures mamillopontine distance and cerebellar width showed excellent diagnostic performance. CONCLUSIONS: Morphometric measures may reliably quantify the morphological distortions of Chiari II malformation on MR images and provide additional tools to assess the severity of Chiari II malformation in clinical and research settings.

Botulinum toxin versus submandibular duct relocation for severe drooling.

AIM: Botulinum neurotoxin type A (BoNT-A) has been described as an effective intervention for drooling and is being increasingly adopted. However, its effectiveness compared with established treatments is still unknown. We undertook a within-participants observational study to examine this. METHOD: An historic cohort was formed of 19 children and young adults (10 males, nine females) with severe drooling who underwent BoNT-A injections followed by surgical re-routing of the submandibular duct at least 6 months later. Mean age at time of admission was 11 years 5 months (range 5-17 y) and mean age at the time of surgery was 14 years (range 6-23 y). Fifteen children were diagnosed with bilateral cerebral palsy (CP), three with unilateral CP, and one with non-progressive developmental delay. Gross Motor Function Classification System levels were the following: level I, n=1; level II, n=2; level III, n=7; level IV, n=6; and level V, n=3). The primary outcome was the drooling quotient, which was assessed before each intervention and 8 and 32 weeks thereafter. A multivariate analysis of variance of repeated measures was performed, with the measurement points as the within-participant variables. RESULTS: The drooling quotient was reduced to a greater extent after surgery than after BoNT-A administration (p=0.001). Compared with a baseline value of 28, the mean drooling quotient 8 weeks after surgery was 10, and 32 weeks after surgery was 4 (p<0.001). Among the group treated with BoNT-A, the drooling quotient showed a significant reduction from a baseline value of 30 to 18 after 8 weeks (p=0.02), and a continued but diminished effect after 32 weeks (drooling quotient 22; p=0.05). INTERPRETATION: Both interventions are effective, but surgery provides a larger and longer-lasting effect.

Thickened saliva after effective management of drooling with botulinum toxin A.

AIM: The aim of this study was to evaluate the rheological properties of saliva after submandibular botulinum toxin type A (BoNT-A) injections. METHOD: We enrolled 15 children (11 males and six females; age range 3-17 y, mean age 9 y 10 mo) diagnosed with spastic (n=9) or dyskinetic (n=6) quadriplegic cerebral palsy (CP); Gross Motor Function Classification System level IV or V; and two children with intellectual disability (IQ<70) who experienced moderate to severe drooling. Salivary flow rate and drooling quotient were measured at baseline and at different times after BoNT-A injections up to 24 weeks. The mucin concentration of saliva was analysed before and after BoNT-A treatment. RESULTS: Both submandibular salivary flow rate (baseline 0.38 mL/min; 24 wks after injection 0.26 mL/min) and drooling quotient (baseline 42.5%; 24 wks 28.80%) were substantially reduced, with a concomitant increase in mucin concentration within 8 weeks after BoNT-A injection (from 0.612 to 1.830 U/mL). The parents of nine children observed thickened saliva. Swallowing and chewing were problematic in seven children. Two of these children needed treatment with mucolytics because of pooling of thickened saliva in the throat. INTERPRETATION: When making decisions about the use of BoNT-A, the risk of problems with masticatory and swallowing functions as a result of thickening of saliva after BoNT-A treatment should be taken into account.

Drooling in cerebral palsy: hypersalivation or dysfunctional oral motor control?

AIM: To investigate whether drooling in children with cerebral palsy (CP) in general and in CP subtypes is due to hypersalivation. METHOD: Saliva was collected from 61 healthy children (30 males, mean age 9y 5mo [SD 11mo]; 31 females, mean age 9y 6mo [1y 2mo]) and 100 children with CP who drooled (57 males, mean age 9y 5mo [3y 11mo], range 3-19y; 43 females, mean age 10y 1mo [4y 9mo], range 4-19y), of whom 53 had spastic, 42 had dyskinetic, and five had ataxic CP. Almost all children were affected bilaterally, and 90 of them were at Gross Motor Function Classification System levels III or higher. The saliva was collected by the swab saliva collection method. The intensity of drooling was evaluated using the drooling quotient. RESULTS: No difference was found in the flow rates, age, or sex between healthy children and children with CP who drooled. On additional subgroup analysis, the flow rates of children with dyskinetic CP differed statistically from those of healthy children (submandibular p=0.047, parotid p=0.040). INTERPRETATION: This study supports the finding in previous studies that no hypersalivation exists in children with CP who drool. Dysfunctional oral motor control seems to be responsible for saliva overflow from the mouth, whereas increased unstimulated salivary flow may occur in children with dyskinetic CP as a result of hyperkinetic oral movements.

Rituximab and intravenous immunoglobulins for relapsing postinfectious opsoclonus-myoclonus syndrome.

We describe 2 children with postinfectious opsoclonus-myoclonus syndrome. Although the patients initially responded to monotherapy with methylprednisolone, intravenous immunoglobulins, or rituximab, they manifested persistent neurologic deficits and relapsing signs. Treatment with rituximab in combination with intravenous immunoglobulin, however, resulted in significant longterm clinical improvement.

Behavioral treatment of drooling: a methodological critique of the literature with clinical guidelines and suggestions for future research.

Many children with mental retardation and developmental disabilities suffer from the consequences of chronic drooling. Behavioral treatment for drooling should be considered before other, more intrusive treatments such as medication and surgery are implemented. However, empirical studies on behavioral procedures are scarce. This article reviews 19 behavioral studies published since 1970. Treatment procedures are (a) instruction, prompting, and positive reinforcement; (b) negative social reinforcement and declarative procedures; (c) cueing techniques; and (d) self-management procedures. Although these procedures yield positive results, critical examination of experimental methodology of the studies reveals several methodological shortcomings. Guidelines for clinical use of behavioral treatment for drooling are presented, and recommendations are given for future research in this area.

Fragmented visuospatial processing in children with pervasive developmental disorder.

Children diagnosed with Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS) and Asperger Syndrome (AS) may be characterised by a similar perceptual focus on details as children with autistic disorder (AD). This was tested by analysing their performance in a visuoperceptual task [the Children's Embedded Figure Test (CEFT)] and a graphic reproduction task [the Rey Complex Figure Task (Rey CFT)]. Control groups were children with Tourette Syndrome (TS) and typically developing children. The TS sample performed similarly to the normal control group in both tasks. The CEFT results did not show the expected preference for local processing in children with PDD-NOS. However, the Rey CFT data revealed that the children with this lesser variant of PDD processed visuospatial information in a fragmented way and were deficient in global processing.

Chronic herpes simplex virus encephalitis in childhood.

Although herpes simplex virus is a major cause of acute encephalitis in childhood, chronic herpes simplex virus encephalitis has only rarely been reported. This report presents a case of chronic herpes simplex virus encephalitis in a 6-year-old female. Diagnosis was based on the detection of herpes simplex virus deoxyribonucleic acid by polymerase chain reaction in combination with the cerebrospinal fluid/serum ratio of herpes simplex virus-specific immunoglobulin G, the presence of herpes simplex virus-specific oligoclonal immunoglobulin G bands in cerebrospinal fluid, and calcifications in the temporal regions found on cerebral computed tomographic scan. Prolonged antiviral therapy was beneficial to later mental development.

Responses to lumbar magnetic stimulation in newborns with spina bifida.

Searching for a tool to quantify motor impairment in spina bifida, transcranial and lumbar magnetic stimulation were applied in affected newborn infants. Lumbar magnetic stimulation resulted in motor evoked potentials in both the quadriceps muscle and the tibialis anterior muscle in most (11/13) subjects. However, transcranial magnetic stimulation did not lead to any response at all. A strong left-to-right correlation existed for amplitude and for latency. Lumbar magnetic stimulation proved to be applicable in newborn infants with spina bifida. Although current concepts regarding spina bifida suppose lower motor neuron dysfunction, the results of this study suggest that lower motor neuron integrity is at least partly preserved after birth. Transcranial magnetic stimulation does not lead to responses in healthy newborn infants because of insufficient synaptogenesis, myelinogenesis, and axon thickness. Therefore, conclusions on upper motor neuron function in spina bifida cannot be drawn. To what extent the method used here can achieve the aim of quantifying motor impairment is a matter of further study.

MR imaging and proton MR spectroscopic studies in Sjögren-Larsson syndrome: characterization of the leukoencephalopathy.

BACKGROUND AND PURPOSE: Sjögren-Larsson syndrome (SLS) is a neurocutaneous syndrome caused by a genetic enzyme deficiency in lipid metabolism. Our purpose was to characterize the nature of the cerebral involvement in SLS. METHODS: MR imaging was performed in 18 patients (aged 5 months to 45 years) and repeated in 14. Single-voxel proton MR spectra were acquired from cerebral white matter and gray matter in 16 patients, with follow-up studies in 11. LCModel fits were used to determine brain metabolite levels. RESULTS: MR imaging showed retardation of myelination and a mild persistent myelin deficit. A zone of increased signal intensity was seen in the periventricular white matter on T2-weighted images. Proton MR spectroscopy of white matter revealed a prominent peak at 1.3 ppm, normal levels of N-acetylaspartate, and elevated levels of creatine (+14%), choline (+18%), and myo-inositol (+54%). MR imaging and proton MR spectroscopy of gray matter were normal. In the two patients examined during the first years of life, abnormalities on MR imaging and proton MR spectroscopy gradually emerged and then stabilized, as in all other patients. CONCLUSION: Abnormalities on MR imaging and proton MR spectroscopy emerge during the first years of life and are similar in all patients with SLS, but the severity varies. The changes are confined to cerebral white matter and suggest an accumulation of lipids, periventricular gliosis, delayed myelination, and a mild permanent myelin deficit.

Assessment of salivary flow rate: biologic variation and measure error.

OBJECTIVE: To investigate the applicability of the swab method in the measurement of salivary flow rate in multiple-handicap drooling children. To quantify the measurement error of the procedure and the biologic variation in the population. STUDY DESIGN: Cohort study. METHODS: In a repeated measurements design, a baseline series of salivary flow rates were obtained from 45 children. The within-subject SD (SW) was calculated to express the measurements error according to a procedure introduced by Bland and Altman. RESULTS: Two hundred twenty-four samples (mean 0.40 mL/min, SD 0.19 mL/min) were obtained and analyzed. The results of this study indicate that consistent scores were obtained at subsequent measurements, and good parity existed between the two measurements of salivary flow rate at each session. The SW could be estimated (0.11 mL/min), which was applied to quantify the specific variation of the salivary flow rate in our population. CONCLUSION: According to Bland and Altman, the SW, which is a quantification of the measurement error and biologic variation, was found to be a useful tool to evaluate the obtained baseline salivary flow rate measurements. The swab method can be used to evaluate salivary flow rates in drooling children with cerebral palsy during interventional studies that aim to reduce saliva production.

The treatment of drooling by ultrasound-guided intraglandular injections of botulinum toxin type A into the salivary glands.

OBJECTIVE: The aim of the study was to present the background, procedure, and technique of bilateral ultrasound-guided, single-dose injections of botulinum toxin type A (BTX) into the salivary glands in patients with severe drooling. STUDY DESIGN: Clinical trial. METHODS: Initially, an in vitro study was performed to determine the volume of the dilution of BTX required for optimal spreading and to gain insight in the spreading pattern of the fluid in the submandibular gland. Subsequently, patients with severe drooling were included in a clinical study. Salivary flow was measured under standardized conditions, and BTX was injected into the submandibular glands with the patient under general anesthesia and with ultrasound guidance as an outpatient procedure or during a short stay at the daytime care unit. RESULTS: BTX for each gland should be diluted in a volume of 1 to 1.5 mL saline to achieve adequate spreading within the gland and to diminish the risk of diffusion into surrounding structures. With ultrasound guidance, separate structures surrounding the glands and structures within the glandular parenchyma are well recognized and injection errors can be avoided. CONCLUSIONS: With the procedure described, it is possible to accurately inject BTX directly into the glandular parenchyma and to visualize spreading of the fluid in the glandular parenchyma. It is found to be a safe method that guarantees an optimal clinical effect and avoids potentially harmful side effects. We recommend ultrasound guidance if injections of BTX into the salivary glands are considered.

Motor evoked potentials and compound muscle action potentials as prognostic tools for neonates with spina bifida.

UNLABELLED: MEPs and CMAPs as prognostic tools for spina bifida. AIM: The aim of this prospective study was to determine the prognostic value of neurophysiological investigations compared to clinical neurological examination in infants with spina bifida. METHODS: Thirty-six neonates born with spina bifida between 2002 and 2007 were evaluated and followed for 2 years. Lumbar motor evoked potentials (MEPs) and compound muscle action potentials (CMAPs) were obtained at the median age of 2 days old before surgical closure of the spinal anomaly. MEPs were recorded from the quadriceps femoris, tibialis anterior, and gastrocnemius muscles and CMAPs from the latter two muscles. Areas under the curve and latencies of the MEPs and CMAPs were measured. Clinical neurological outcome at the age of 2 years was described using Muscle Function Classes (MFCs) and ambulation status. RESULTS: The areas under the curve of MEPs and CMAPs in the legs were associated with lower neonatal levels of motor and sensory impairment. Better muscle function class of the lower limbs at 2 years of age was associated with larger MEP and CMAP areas of the gastrocnemius and tibialis anterior muscles at neonatal age. DISCUSSION: MEPs and CMAPs of the gastrocnemius and tibialis anterior muscles are of prognostic value for clinical neurological outcome in neonates born with spina bifida.

Motor sequence learning in children with spina bifida.

Cognitive and motor problems are common in children with spina bifida (SB), particularly in those children with cerebral malformations (SBM). Little is known about how these conditions affect motor learning. This study examines motor sequence learning in children with SB, SBM, and healthy controls. Assessment consisted of neuropsychological tests, a simple drawing task, and a spatial motor sequence learning task. Implicit motor learning was unaffected in children with SB(M), and their sequence learning ability was also similar to that of controls. However, both groups (SB and SBM) showed impaired motor performance. The role of cerebellar malformation with SB(M) is discussed.

What could predict effectiveness of Botulinum Toxin to treat drooling: a search for evidence of discriminatory factors on the level of body functions or structures.

BACKGROUND: The treatment of drooling is important to families that experience the daily impact and research to elucidate clinical factors that play a role in the outcome of drooling treatment should be encouraged. AIM: To define clinical factors that influence therapy outcome of submandibular Botulinum Toxin (BoNT-A) injections for drooling. METHODS: Prospectively collected data of 128 children with cerebral palsy were evaluated; 80 spastic and 48 dyskinetic movement disorder, mostly Gross Motor Function Classification System III and higher; over 70% had an IQ <70. In addition, 23 fully ambulant children with exclusively intellectual disability were treated for drooling by ultrasound-guided injections of BoNT-A into the submandibular glands. Salivary flow rates and drooling quotients were measured at baseline and at 8 weeks after injection. Extensive information about the oral motor performance was gathered. Successful clinical response was defined as a 50% reduction of the baseline Drooling Quotient; 85 children were responsive to BoNT-A and 66 children unresponsive. RESULTS: Five nominated clinical factors that possibly could influence saliva reduction (head position, lip seal, voluntary control over the tongue, control of voluntary movement functions, and mental age) did not influence the responsiveness to BoNT-A. INTERPRETATION: Other variables need to be considered to predict the outcome of BoNT-A treatment. This article describes the first attempt to reveal the contribution of body functions and structures to the outcome of BoNT-A submandibular injections.

Influence of birth mode on early neurological outcome in infants with myelomeningocele.

OBJECTIVE: The aim of the study was to determine whether route of birth affects early neurological outcome in infants with myelomeningocele. STUDY DESIGN: In a retrospective cohort study, 95 neonates with myelomeningocele evaluated at the Radboud University Nijmegen Medical Centre between 1990 and 2006 were reviewed. The effect of delivery mode on early neurological outcome was assessed as the difference between the functional neurological level of the defect and the X-ray level (ΔFAX). RESULTS: Early neurological outcome was better in the vaginally delivered infants (ΔFAX 0.96 ± 2.1) than in those delivered by cesarean section (ΔFAX 0.20 ± 2.5). After correction for confounders, multiple regression analysis demonstrated that vaginal delivery was associated with significantly better early neurological outcome as compared to cesarean section (ß=1.21; 95% CI 0.16; 2.27; p=0.03) for infants in vertex and breech position combined. Subgroup analysis revealed a non-significant trend towards better outcome after vaginal delivery that was more pronounced in infants in breech position than in vertex position. CONCLUSION: In infants with myelomeningocele, born in either vertex or breech position, there is no clinical evidence that early neurological outcome is improved by cesarean section.