Reproducibility of maximal and submaximal exercise testing in "normal ambulatory" and "community ambulatory" children and adolescents with spina bifida: which is best for the evaluation and application of exercise training?

BACKGROUND: With emerging interest in exercise and lifestyle interventions for children and adolescents with spina bifida, there is a need for appropriate measurements in exercise testing. OBJECTIVE: The purpose of this study was to assess both reliability and agreement of maximal and submaximal exercise measures in "normal ambulatory" and "community ambulatory" children and adolescents with spina bifida. DESIGN: This was a reproducibility study. METHODS: Twenty-three children and adolescents with spina bifida (10 normal ambulatory and 13 community ambulatory) participated in the study. Maximal exercise outcomes were measured using a graded treadmill test. Peak measures (peak oxygen uptake [V(O2)peak], peak heart rate [HRpeak], heart rate response [HRR], and oxygen pulse) were recorded. For submaximal measures, heart rate (HR) and oxygen uptake (V(O2)) at the ventilatory threshold and oxygen uptake efficiency slope (OUES) were derived from the maximal measures. Functional performance was measured as the 6-minute walking distance and the maximal speed during the treadmill test. After checking for normality and heteroscedasticity, paired t tests, intraclass correlation coefficients (ICCs), and the smallest detectable difference (SDD) or the coefficient of variation (CV) were calculated. RESULTS: Performance measures showed good reliability and agreement. For maximal measures, acceptable ICCs were found for all measures. For submaximal measures, only HR at the ventilatory threshold showed an ICC of less than .80. Agreement showed a CV of less than 10% for all measures, except for V(O2) at the ventilatory threshold, HRR, and OUES. LIMITATIONS: Limitations of the study include missing data due to equipment failure. Furthermore, the outcomes were limited to normal ambulatory and community ambulatory children and adolescents with spina bifida. CONCLUSIONS: Both maximal and submaximal measures of exercise testing can be used for discriminative purposes in ambulatory children and adolescents with spina bifida. For evaluative purposes, HR measures are superior to V(O2) measures, while taking into account the individual variation of 5% to 8%. The SDD was 0.5 km/h for peak speed and 36.3 m for 6-minute walking distance. Heart rate response, oxygen pulse, and OUES are not recommended in the evaluation of exercise testing in this population.

Noninvasive detection of the distinction between progressive and compensated hydrocephalus in infants: is it possible?

OBJECT: Clinical signs and symptoms of hydrocephalus can be clear and specific, but also subtle, nonspecific, or even absent. It may be difficult to decide whether shunt placement is indicated, especially in infants. Therefore, there is a need for the development of better noninvasive detection methods to distinguish between compensated and (slowly) progressive hydrocephalus. Early interference can reverse the cerebral damage, whereas the detection of a nonpathological state in infants with compensated hydrocephalus avoids the complications of unnecessary shunt procedures. Using MR imaging, the authors investigated cerebral blood flow (CBF) and apparent diffusion coefficients (ADCs) measured in infants with clinically compensated hydrocephalus. METHODS: The diagnosis of compensated hydrocephalus was made on the basis of clinical criteria, consisting of no signs or symptoms of increased intracranial pressure (ICP), measurement of a normal ICP, and standard MR imaging showing enlarged ventricles. Flow measurements through both internal carotid arteries and the basilar artery were considered to represent the total CBF. In addition, ADC values were assessed in 5 different regions of interest in the brain parenchyma using diffusion weighted imaging. Brain volumetric measurement was performed to express CBF in ml/100 cm(3) brain/min, thus compensating for physiological CBF growth over time. Mean arterial blood pressure was manually measured to exclude this factor as a cause of a possible change in CBF. Intracranial pressure measurement was performed noninvasively using the Rotterdam Teletransducer. RESULTS: Eighteen infants with clinically compensated hydrocephalus were included. The mean CBF was 53.5 ml/100 cm(3) of brain/min. The individual CBF values were graphically compared with age-related normal CBF values and fell in the normal range. Mean ADC value was 890.0 x10(-6) mm(2)/sec. Apparent diffusion coefficient values per region of interest were graphically compared with normal ADC values per region of interest and fell within the normal range. CONCLUSIONS: In infants with hydrocephalus, normal CBF and low ADC values, as measured using MR imaging, are associated with compensated hydrocephalus and may support a conservative approach with respect to the decision on whether to place a shunt.

Is cognitive functioning associated with subjective quality of life in young adults with spina bifida and hydrocephalus?

OBJECTIVE: To test the hypothesis that cognitive functioning is associated with subjective quality of life of young adults with spina bifida and hydrocephalus (SBHC). DESIGN: Cross-sectional multi-centre study in The Netherlands. SUBJECTS: A total of 110 young adults with SBHC (16-25 years old, 63% female). METHODS: Cognitive domains measured were intelligence (Raven Standard Progressive Matrices), memory (Wechsler Memory Scale) and executive functioning (Wisconsin modified Card Sorting Test (WmCST), Trail Making Test A and B (TMT) and UNKA word production test). Subjective quality of life was measured with a visual analogue scale. Correlations and hierarchical regression analysis controlling for age, gender and functional independence were applied. RESULTS: The TMT score was significantly associated (-0.25) with subjective quality of life. In the hierarchical regression analysis both the WmCST and TMT scores were significant determinants of subjective quality of life (Beta values 0.24 and -0.31 respectively). Intelligence, memory and word production were not related to subjective quality of life. All 5 cognitive variables together explained a significant additional 14.6% of the variance of subjective quality of life (total explained variance 19.9%). CONCLUSION: Executive functioning was associated with subjective quality of life in young adults with spina bifida and hydrocephalus. This finding underlines the importance of examining cognitive functioning of persons with SBHC in addition to medical and functional status in medical care and outcome research.

New transcranial Doppler index in infants with hydrocephalus: transsystolic time in clinical practice.

Raised intracranial pressure (ICP) in infants with hydrocephalus may cause (ir)reversible damage to the brain parenchyma but can be present without clinical signs and/or symptoms. Therefore, new, favorably noninvasive, detection methods are needed to distinguish between compensated hydrocephalus with normal intracranial pressure and slowly progressive hydrocephalus with increased intracranial pressure. Because early ischemic changes in the brain parenchyma are associated with increased intracranial pressure, transcranial Doppler (TCD) indices may be useful to detect increased intracranial pressure in infants with hydrocephalus. Twenty-four infants with hydrocephalus underwent noninvasive ICP measurement, magnetic resonance imaging and TCD before and after cerebrospinal fluid (CSF) diversion. The TCD indices were paired to the anterior fontanelle pressure findings and compared for correlation. After CSF diversion, ICP decreased significantly from 21.8 cm H(2)O to 7.7 cm H(2)O (p<0.005). The transsystolic time (TST) as measured with TCD increased significantly from 176 to 221 ms (p<0.005), whereas the pulsatility index (PI) decreased significantly from 1.3 to 1.0 (p<0.05). The resistance index (RI) decreased significantly from 0.73 to 0.63 (p<0.05). Mean bloodflow velocity through the middle cerebral artery increased significantly from 55.5 to 75.8 cm/s (p<0.005). TST has a strong correlation with the ICP (p<0.005). Measuring TST with TCD can be helpful in the decision-making process about whether to perform CSF diversion in infants with hydrocephalus. Because TST is related solely to the relative changes in the flow velocity caused by intracranial physical properties, it has a closer relation to ICP than the PI and the RI.

Longitudinal diffusion-weighted imaging in infants with hydrocephalus: decrease in tissue water diffusion after cerebrospinal fluid diversion.

OBJECT: Progressive hydrocephalus may lead to edema of the periventricular white matter and to damage of the brain parenchyma because of compression, stretching, and ischemia. The aim of the present study was to investigate whether cerebral edema can be quantified using diffusion-weighted imaging in infants with hydrocephalus and whether CSF diversion could decrease cerebral edema. METHODS: Diffusion-weighted MR imaging was performed in 24 infants with progressive hydrocephalus before and after CSF diversion. Parametric images of the trace apparent diffusion coefficients (ADCs) were obtained. The ADCs of 5 different cortical and subcortical regions of interest were calculated pre- and postoperatively in each patient. The ADC values were compared with age-related normal values. Mean arterial blood pressure and anterior fontanel pressure were measured immediately after each MR imaging study. RESULTS: After CSF diversion, the mean ADC decreased from a preoperative value of 1209 +/- 116 x 10(-6) mm(2)/second to a postoperative value of 928 +/- 64 x 10(-6) mm(2)/second (p < 0.005). Differences between pre- and postoperative ADC values were most prominent in the periventricular white matter, supporting the existence of preoperative periventricular edema. Compared with age-related normal values, the preoperative ADC values were higher and the postoperative ADC values were lower, although within normal range. The decrease in ADC after CSF drainage was more rapid than the more gradual physiological decrease that is related to age. The preoperative ICP was elevated in all patients. After CSF diversion the ICP decreased significantly to within the normal range. A linear correlation between ADC values and ICP was found (correlation coefficient 0.496, p < 0.001). In all patients the mean arterial blood pressure was within physiological limits both pre- and postoperatively. CONCLUSIONS: This study shows a rapid and more extensive decrease in ADC values after CSF diversion than is to be expected from physiological ADC decrease solely due to increasing patient age. The preoperative ADC increase can be explained by interstitial edema caused by transependymal CSF leakage or by vasogenic edema caused by capillary compression and stretching of the brain parenchyma. This study population of infants with (early recognized) hydrocephalus did not suffer from cytotoxic edema. These findings may help to detect patients at risk for cerebral damage by differentiating between progressive and compensated hydrocephalus.

Treadmill testing of children who have spina bifida and are ambulatory: does peak oxygen uptake reflect maximum oxygen uptake?

BACKGROUND: Earlier studies have demonstrated low peak oxygen uptake ((.)Vo(2)peak) in children with spina bifida. Low peak heart rate and low peak respiratory exchange ratio in these studies raised questions regarding the true maximal character of (.)Vo(2)peak values obtained with treadmill testing. OBJECTIVE: The aim of this study was to determine whether the Vo(2)peak measured during an incremental treadmill test is a true reflection of the maximum oxygen uptake ((.)Vo(2)max) in children who have spina bifida and are ambulatory. DESIGN: A cross-sectional design was used for this study. METHODS: Twenty children who had spina bifida and were ambulatory participated. The (.)Vo(2)peak was measured during a graded treadmill exercise test. The validity of (.)Vo(2)peak measurements was evaluated by use of previously described guidelines for maximum exercise testing in children who are healthy, as well as differences between Vo(2)peak and (.)Vo(2) during a supramaximal protocol ((.)Vo(2)supramaximal). RESULTS: The average values for (.)Vo(2)peak and normalized (.)Vo(2)peak were, respectively, 1.23 L/min (SD=0.6) and 34.1 mL/kg/min (SD=8.3). Fifteen children met at least 2 of the 3 previously described criteria; one child failed to meet any criteria. Although there were no significant differences between (.)Vo(2)peak and Vo(2)supramaximal, 5 children did show improvement during supramaximal testing. LIMITATIONS: These results apply to children who have spina bifida and are at least community ambulatory. CONCLUSIONS: The (.)Vo(2)peak measured during an incremental treadmill test seems to reflect the true (.)Vo(2)max in children who have spina bifida and are ambulatory, validating the use of a treadmill test for these children. When confirmation of maximal effort is needed, the addition of supramaximal testing of children with disability is an easy and well-tolerated method.

Magnetic resonance imaging for quantitative flow measurement in infants with hydrocephalus: a prospective study.

OBJECT: Raised intracranial pressure (ICP) that is associated with hydrocephalus may lead to alterations in cerebral hemodynamics and ischemic changes in the brain. In infants with hydrocephalus, defining the right moment for surgical intervention based on clinical signs alone can sometimes be a difficult task. Clinical signs of raised ICP are known to be unreliable and sometimes even misleading. Furthermore, when sutures are closed, ICP does not always correlate with the size of the ventricles or with the clinical signs or symptoms. In this study the authors investigated whether cerebral blood flow (CBF) can be measured by using quantitative MR angiography in infants with progressive hydrocephalus. In addition, the authors investigated the relationship between CBF and ICP, before and after cerebrospinal fluid (CSF) diversion. METHODS: Fifteen infants with progressive hydrocephalus (age range 1 day-7 months) were examined. All patients underwent anterior fontanel pressure measurement, MR angiography, and mean arterial blood pressure measurements before and after CSF diversion. Brain volume was measured to compensate for the physiological increase in CBF during brain maturation in infants. RESULTS: The mean preoperative ICP was 19.1 +/- 8.4 cm H(2)O (+/- standard deviation). The mean postoperative ICP was 6.7 +/- 4.0 cm H(2)O (p < 0.005). The mean preoperative CBF was 25.7 +/- 11.3 ml/100 cm(3) brain/min. After CSF diversion, CBF increased to 50.1 +/- 12.1 ml/100 cm(3) brain/min (p < 0.005). The mean arterial blood pressure did not change after surgical intervention. CONCLUSIONS: Magnetic resonance imaging can be used to measure CBF in infants with hydrocephalus. Raised ICP was related to a decrease in CBF. After CSF diversion, CBF and ICP improved to values within the normal range.

Outcome in pediatric hydrocephalus: a comparison between previously used outcome measures and the hydrocephalus outcome questionnaire.

OBJECT: The objectives of this study were to assess, in a cohort of children with recently treated hydrocephalus, the correlation between scores on the Hydrocephalus Outcome Questionnaire (HOQ) and the children's type of schooling and motor functioning, and to assess the overall outcome of the children. METHODS: The health status of 142 pediatric patients (85 boys) with previous hydrocephalus, born between 1995 and 1999, was assessed. Outcomes were determined using the HOQ, type of schooling, and motor functioning. Data were obtained from parental interviews and patient medical records. RESULTS. Twelve patients died (8.5%). Responses to the HOQ were obtained from 107 patients (65 boys). The mean age of the patients was 7 years and 9 months +/- 1.42 years (range 6-10 years). The Physical Health score of the HOQ correlated well with the motor functioning score (r = 0.652) as did the Cognitive Health score with the type of schooling (r = 0.672). Fifty-nine percent of the patients were able to attend a school for students with normal intelligence. Disabling motor functioning was found in only 30% of patients. Epilepsy was present in 14%. CONCLUSIONS: The results show a good correlation between the type of schooling and the Cognitive HOQ score and between the Physical HOQ score and the motor functioning score. The HOQ is a simple and very useful measurement for determining outcome in pediatric hydrocephalus.

Neurological outcome in isolated congenital heart block and hydrops fetalis.

OBJECTIVE: Isolated fetal heart block (HB), a condition associated with fetal hydrops, carries a high mortality rate and may result in neurodevelopmental sequelae. To the best of our knowledge, no data exist regarding the long-term outcome of such hydropic fetuses. We reviewed our experience with this condition to determine the neurodevelopmental outcome of prenatally diagnosed cases with isolated HB complicated by hydrops fetalis. METHODS: Neurodevelopmental assessment of 5 children presented prenatally with isolated HB associated with hydrops fetalis. RESULTS: During the last 18 years, 10 cases were detected prenatally with isolated HB and hydrops fetalis. 3 of the 10 fetuses died in utero, and 2 died postnatally, due to a dilated cardiomyopathy, at the age of 9 months and 4 years, respectively. Neurodevelopmental studies done on the 5 remaining children were normal. CONCLUSION: Long-term neurodevelopmental assessments of 5 surviving cases presented prenatally with isolated HB and hydrops fetalis are reassuring.

Sumatriptan nasal spray in the acute treatment of migraine in adolescents and children.

About 4-10% of children and adolescents suffer from migraine. In the last few years, several studies have been performed to assess the efficacy and safety of triptans for the acute treatment of migraine in children and adolescents. Only sumatriptan nasal spray has been approved for the treatment of acute migraine with or without aura in adolescents aged 12-17 years in Europe. This review describes the results of the studies with sumatriptan nasal spray that have been performed in children and adolescents, including a study performed in the Netherlands.

MRI, volumetry, 1H spectroscopy, and cerebropetal blood flowmetry in childhood idiopathic anatomic megalencephaly.

PURPOSE: To evaluate cerebral abnormalities in childhood idiopathic anatomic megalencephaly (MC) by means of different magnetic resonance (MR) modalities. MATERIALS AND METHODS: MRI, volumetry, spectroscopy, and cerebropetal blood flowmetry were performed in six children with idiopathic anatomic MC, and seven volunteers. RESULTS: MRI revealed an increased ventricular system in five of six patients. A thalamic hamartoma was found in one patient and a Chiari I malformation was found in two. Volumetric analysis showed a disproportional increase of ventricular volume but normal subarachnoid cerebrospinal fluid (CSF) volume. Supratentorial volume was disproportionally increased compared to cerebellar volume. Intracranial volume correlated significantly with skull circumference. MR spectroscopy (MRS) N-acetyl aspartate/choline (NAA/Cho) peak ratios in WM were significantly higher in patients than in controls. Choline/creatine (Cho/Cr) peak ratios in WM were significantly lower in patients. Cortical gray matter (GM) MRS ratios were unaltered. Cerebropetal flow was increased in MC, possibly related to increased brain volume. CONCLUSION: This study reveals associated developmental anomalies for idiopathic anatomic MC. A relative ventriculomegaly was found, which should not be misinterpreted as true hydrocephalus. In contrast to metabolic MC, MRS showed no severe disturbances. Total intracranial volume is correlated to skull circumference and cerebropetal blood flow.

Functional independence among young adults with spina bifida, in relation to hydrocephalus and level of lesion.

Knowledge about the level of functional independence that can be expected in adulthood might support decisions on the treatment of newborn infants with spina bifida. This study determined functional independence among young adults with spina bifida and its relationships with pathological characteristics known from birth (hydrocephalus and level of lesion). Data were collected from medical records and by physical examination. Functional independence was assessed on six domains (self-care, sphincter control, transfers, locomotion, communication, and social cognition) using the Functional Independence Measure (FIM). Participants were 165 patients with spina bifida (69 males, 96 females; age range 16 to 25y, mean 20y 9mo [SD 2.9]; 117 with hydrocephalus). Patients without hydrocephalus were independent for all FIM domains except sphincter control, as were patients with hydrocephalus with a lesion level below L2. Most patients with hydrocephalus and a lesion at L2 or above were dependent as regards sphincter control (98%), locomotion (79%), and self-care (54%), and quite a few needed support in transfers (38%), social cognition (29%), and communication (15%).

Cerebral, cerebellar, and colobomatous anomalies in three related males: Sex-linked inheritance in a newly recognized syndrome with features overlapping with Joubert syndrome.

We present a so far unrecognized X-linked mental retardation syndrome with features overlapping with Joubert syndrome (JBS). Two brothers showed hypotonia, mental retardation, ocular abnormalities with impaired vision and colobomas and a breathing pattern compatible with JBS. Neuroimaging revealed cerebellar vermis hypoplasia and ventriculomegaly. A tentative diagnosis of JBS was made, and autosomal recessive inheritance considered most likely. In a subsequent pregnancy that occurred after artificial donor insemination, ultrasound in the 22nd week revealed a Dandy-Walker malformation and hydrocephaly. At autopsy at 34 weeks of gestation, the male infant showed cerebellar vermis aplasia and abnormalities of the brainstem and cerebral cortex. He was considered to have the same disorder as his two half-brothers. This renders the pedigree highly suggestive of X-linked inheritance. The clinical symptoms of this syndrome resemble JBS. However, the absence of the molar tooth sign and the X-linked inheritance do not support JBS. We propose the name X-linked cerebral-cerebellar-coloboma syndrome to distinguish the two disorders. Differentiation of the two disorders is especially important in genetic counseling, where artificial donor insemination may be considered as a means of reducing the recurrence risk, or when female relatives of the patient are concerned.

1H magnetic resonance spectroscopy in human hydrocephalus.

PURPOSE: To evaluate cerebral metabolism in clinical hydrocephalus with (1)H magnetic resonance spectroscopy (MRS). MATERIALS AND METHODS: In 24 children and adults with progressive, arrested, or normal pressure hydrocephalus, long-echo time (1)H MR spectra were acquired from periventricular white matter and intraventricular cerebrospinal fluid (CSF). Metabolite ratios, and the presence of lactate, were compared with 38 age-matched controls. RESULTS: Metabolite ratios of patients were within the 95% confidence interval (CI) of controls. A small lactate resonance was detected in 20% of control and hydrocephalic subjects. Lactate was consistently visible in CSF spectra, though lactate concentrations were normal. The CSF lactate T(2) was long in comparison with the known intracellular metabolite T(2) relaxation times. In three neonates with hydrocephalus and spina bifida, 3-hydroxybutyrate was detected in CSF in vivo. CONCLUSION: Within the limits of the present methods, (1)H MRS could not detect cerebral metabolic abnormalities in human hydrocephalus and provided no additional diagnostic information. The long T(2) of lactate in CSF explains its high visibility. Hence, the detection of lactate in spectra acquired from voxels that contain CSF does not necessarily imply cerebral ischemia.