Functional electrical stimulation of the ankle dorsiflexors during walking in spastic cerebral palsy: a systematic review.

AIM: To assess the effect of functional electrical stimulation (FES) of ankle dorsiflexors in children and adolescents with spastic cerebral palsy (CP) during walking. METHOD: A systematic review was performed using the American Academy of Cerebral Palsy and Developmental Medicine methodology and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Six databases were searched for studies applying interventions to patients aged younger than 20 years. Outcomes were classified according to the International Classification of Functioning, Disability and Health (ICF). RESULTS: Seven hundred and eighty abstracts were found, 35 articles were fully screened, and 14 articles were used for analysis. Only five articles (three studies) were of level I to III evidence. At ICF participation and activity level, there is limited evidence for a decrease in self-reported frequency of toe-drag and falls. At ICF body structure and function level, there is clear evidence (I-III) that FES increased (active) ankle dorsiflexion angle, strength, and improved selective motor control, balance, and gait kinematics, but decreased walking speed. Adverse events include skin irritation, toleration, and acceptation issues. INTERPRETATION: There are insufficient data supporting functional gain by FES on activity and participation level. However, evidence points towards a role for FES as an alternative to orthoses in children with spastic CP. WHAT THIS PAPER ADDS: Effects of functional electrical stimulation (FES) point towards a potential role as an alternative to orthoses for patients with spastic cerebral palsy (CP). Some evidence for a decrease in self-reported frequency of toe-drag and falls with the use of FES in spastic CP. Limited evidence for improvements in activity and participation in patients with spastic CP using FES.

Noninvasive treatment alternative for intractable startle epilepsy.

We describe a treatment alternative for intractable, startle-provoked, epileptic seizures in four children aged between 8 and 14. Three of the four children had symptomatic localization-related epilepsy. They all suffered from intractable epilepsy precipitated by sudden sounds. The fact that seizures tended to occur with high frequency - more than one seizure a day - had a clear impact on daily life. Clinical seizure pattern demonstrated asymmetric tonic posturing in all four children. Three children experienced several seizure types including focal seizure onset. All children had focal neurological signs or learning disabilities or a combination of both. Our noninvasive treatment method using psychoeducational counseling and sound generators was applied in four children, resulting in a seizure frequency reduction of ≥ 50% in two of them.

Reduced structural connectivity between sensorimotor and language areas in rolandic epilepsy.

INTRODUCTION: Rolandic epilepsy (RE) is a childhood epilepsy with centrotemporal (rolandic) spikes, that is increasingly associated with language impairment. In this study, we tested for a white matter (connectivity) correlate, employing diffusion weighted MRI and language testing. METHODS: Twenty-three children with RE and 23 matched controls (age: 8-14 years) underwent structural (T1-weighted) and diffusion-weighted MRI (b = 1200 s/mm(2), 66 gradient directions) at 3T, as well as neuropsychological language testing. Combining tractography and a cortical segmentation derived from the T1-scan, the rolandic tract were reconstructed (pre- and postcentral gyri), and tract fractional anisotropy (FA) values were compared between patients and controls. Aberrant tracts were tested for correlations with language performance. RESULTS: Several reductions of tract FA were found in patients compared to controls, mostly in the left hemisphere; the most significant effects involved the left inferior frontal (p = 0.005) and supramarginal (p = 0.004) gyrus. In the patient group, lower tract FA values were correlated with lower language performance, among others for the connection between the left postcentral and inferior frontal gyrus (p = 0.043, R = 0.43). CONCLUSION: In RE, structural connectivity is reduced for several connections involving the rolandic regions, from which the epileptiform activity originates. Most of these aberrant tracts involve the left (typically language mediating) hemisphere, notably the pars opercularis of the inferior frontal gyrus (Broca's area) and the supramarginal gyrus (Wernicke's area). For the former, reduced language performance for lower tract FA was found in the patients. These findings provide a first microstructural white matter correlate for language impairment in RE.

Aberrant functional connectivity between motor and language networks in rolandic epilepsy.

INTRODUCTION: Rolandic epilepsy (RE) is an idiopathic focal childhood epilepsy with a well-established neuropsychological profile of language impairment. The aim of this study is to provide a functional correlate that links rolandic (sensorimotor) pathology to language problems using functional MRI. MATERIALS AND METHODS: Twenty-three children with RE (8-14 years old) and 21 matched controls underwent extensive language assessment (Clinical Evaluation of Language Fundamentals). fMRI was performed at rest and using word generation, reading, and finger tapping paradigms. Since no activation group differences were found, regions of interest (ROIs) were defined at pooled (patients and controls combined) activation maxima and in contralateral homotopic cortex, and used to assess language lateralization as well as for a resting-state connectivity analysis. Furthermore, the association between connection strength and language performance was investigated. RESULTS: Reduced language performance was found in the children with RE. Bilateral activation was found for both language tasks with some predominance of the left hemisphere in both groups. Compared to controls, patient connectivity was decreased between the left sensorimotor area and right inferior frontal gyrus (p<0.01). For this connection, lower connectivity was associated with lower language scores in the patient group (r=0.49, p=0.02), but not in the controls. CONCLUSION: Language laterality analysis revealed bilateral language representation in the age range under study (8-14 years). As a consequence, the connection of reduced functional connectivity we found represents an impaired interplay between motor and language networks, and aberrant functional connectivity associated with poorer language performance. These findings provide a first neuronal correlate in terms of aberrant resting-state functional connectivity for language impairment in RE.

Reduced functional integration of the sensorimotor and language network in rolandic epilepsy.

INTRODUCTION: Over the last years, evidence has accumulated that rolandic epilepsy (RE) is associated with serious cognitive comorbidities, including language impairment. However, the cerebral mechanism through which epileptiform activity in the rolandic (sensorimotor) areas may affect the language system is unknown. To investigate this, the connectivity between rolandic areas and regions involved in language processing is studied using functional MRI (fMRI). MATERIALS AND METHODS: fMRI data was acquired from 22 children with rolandic epilepsy and 22 age-matched controls (age range: 8-14 years), both at rest and using word-generation and reading tasks. Activation map analysis revealed no group differences (FWE-corrected, p < 0.05) and was therefore used to define regions of interest for pooled (patients and controls combined) language activation. Independent component analysis with dual regression was used to identify the sensorimotor resting-state network in all subjects. The associated functional connectivity maps were compared between groups at the regions of interest for language activation identified from the task data. In addition, neuropsychological language testing (Clinical Evaluation of Language Fundamentals, 4th edition) was performed. RESULTS: Functional connectivity with the sensorimotor network was reduced in patients compared to controls (p = 0.011) in the left inferior frontal gyrus, i.e. Broca's area as identified by the word-generation task. No aberrant functional connectivity values were found in the other regions of interest, nor were any associations found between functional connectivity and language performance. Neuropsychological testing confirmed language impairment in patients relative to controls (reductions in core language score, p = 0.03; language content index, p = 0.01; receptive language index, p = 0.005). CONCLUSION: Reduced functional connectivity was demonstrated between the sensorimotor network and the left inferior frontal gyrus (Broca's area) in children with RE, which might link epileptiform activity/seizures originating from the sensorimotor cortex to language impairment, and is in line with the identified neuropsychological profile of anterior language dysfunction.

Early onset of cortical thinning in children with rolandic epilepsy.

INTRODUCTION: Rolandic epilepsy, a childhood epilepsy associated with language impairments, was investigated for language-related cortical abnormalities. METHODS: Twenty-four children with rolandic epilepsy and 24 controls (age 8-14 years) were recruited and underwent the Clinical Evaluation of Language Fundamentals test. Structural MRI was performed at 3 T (voxel size 1 × 1 × 1 mm(3)) for fully automated quantitative assessment of cortical thickness. Regression analysis was used to test for differences between patients and controls and to assess the effect of age and language indices on cortical thickness. RESULTS: For patients the core language score (mean ± SD: 92 ± 18) was lower than for controls (106 ± 11, p = 0.0026) and below the norm of 100 ± 15 (p = 0.047). Patients showed specific impairments in receptive language index (87 ± 19, p = 0.002) and language content index (87 ± 18, p = 0.0016). Cortical thickness was reduced in patients (p < 0.05, multiple-comparisons corrected) in left perisylvian regions. Furthermore, extensive cortical thinning with age was found in predominantly left-lateralized frontal, centro-parietal and temporal regions. No associations were found between cortical thickness and language indices in the regions of aberrant cortex. CONCLUSION: The cortical abnormalities described represent subtle but significant pathomorphology in this critical phase of brain development (8-14 years) and suggest that rolandic epilepsy should not be considered merely a benign condition. Future studies employing longitudinal designs are prompted for further investigations into cerebral abnormalities in RE and associations with cognitive impairment and development.

Intrathecal baclofen treatment in dystonic cerebral palsy: a randomized clinical trial: the IDYS trial.

BACKGROUND: Dystonic cerebral palsy is primarily caused by damage to the basal ganglia and central cortex. The daily care of these patients can be difficult due to dystonic movements. Intrathecal baclofen treatment is a potential treatment option for dystonia and has become common practice. Despite this widespread adoption, high quality evidence on the effects of intrathecal baclofen treatment on daily activities is lacking and prospective data are needed to judge the usefulness and indications for dystonic cerebral palsy. The primary aim of this study is to provide level one clinical evidence for the effects of intrathecal baclofen treatment on the level of activities and participation in dystonic cerebral palsy patients. Furthermore, we hope to identify clinical characteristics that will predict a beneficial effect of intrathecal baclofen in an individual patient. METHODS/DESIGN: A double blind placebo-controlled multi-center randomized clinical trial will be performed in 30 children with dystonic cerebral palsy. Patients aged between 4 and 25 years old with a confirmed diagnosis of dystonic cerebral palsy, Gross Motor Functioning Classification System level IV or V, with lesions in the cerebral white matter, basal ganglia or central cortex and who are eligible for intrathecal baclofen treatment will be included. Group A will receive three months of continuous intrathecal baclofen treatment and group B will receive three months of placebo treatment, both via an implanted pump. After this three month period, all patients will receive intrathecal baclofen treatment, with a follow-up after nine months. The primary outcome measurement will be the effect on activities of and participation in daily life measured by Goal Attainment Scaling. Secondary outcome measurements on the level of body functions include dystonia, spasticity, pain, comfort and sleep-related breathing disorders. Side effects will be monitored and we will study whether patient characteristics influence outcome. DISCUSSION: The results of this study will provide data for evidence-based use of intrathecal baclofen in dystonic cerebral palsy.

Brain white matter oedema due to ClC-2 chloride channel deficiency: an observational analytical study.

BACKGROUND: Mutant mouse models suggest that the chloride channel ClC-2 has functions in ion and water homoeostasis, but this has not been confirmed in human beings. We aimed to define novel disorders characterised by distinct patterns of MRI abnormalities in patients with leukoencephalopathies of unknown origin, and to identify the genes mutated in these disorders. We were specifically interested in leukoencephalopathies characterised by white matter oedema, suggesting a defect in ion and water homoeostasis. METHODS: In this observational analytical study, we recruited patients with leukoencephalopathies characterised by MRI signal abnormalities in the posterior limbs of the internal capsules, midbrain cerebral peduncles, and middle cerebellar peduncles from our databases of patients with leukoencephalopathies of unknown origin. We used exome sequencing to identify the gene involved. We screened the candidate gene in additional patients by Sanger sequencing and mRNA analysis, and investigated the functional effects of the mutations. We assessed the localisation of ClC-2 with immunohistochemistry and electron microscopy in post-mortem human brains of individuals without neurological disorders. FINDINGS: Seven patients met our inclusion criteria, three with adult-onset disease and four with childhood-onset disease. We identified homozygous or compound-heterozygous mutations in CLCN2 in three adult and three paediatric patients. We found evidence that the CLCN2 mutations result in loss of function of ClC-2. The remaining paediatric patient had an X-linked family history and a mutation in GJB1, encoding connexin 32. Clinical features were variable and included cerebellar ataxia, spasticity, chorioretinopathy with visual field defects, optic neuropathy, cognitive defects, and headaches. MRI showed restricted diffusion suggesting myelin vacuolation that was confined to the specified white matter structures in adult patients, and more diffusely involved the brain white matter in paediatric patients. We detected ClC-2 in all components of the panglial syncytium, enriched in astrocytic endfeet at the perivascular basal lamina, in the glia limitans, and in ependymal cells. INTERPRETATION: Our observations substantiate the concept that ClC-2 is involved in brain ion and water homoeostasis. Autosomal-recessive CLCN2 mutations cause a leukoencephalopathy that belongs to an emerging group of disorders affecting brain ion and water homoeostasis and characterised by intramyelinic oedema. FUNDING: European Leukodystrophies Association, INSERM and Assistance Publique-Hôpitaux de Paris, Dutch Organisation for Scientific Research (ZonMw), E-Rare, Hersenstichting, Optimix Foundation for Scientific Research, Myelin Disorders Bioregistry Project, National Institute of Neurological Disorders and Stroke, and Genetic and Epigenetic Networks in Cognitive Dysfunction (GENCODYS) Project (funded by the European Union Framework Programme 7).

Increased number of cerebellar granule cells and astrocytes in the internal granule layer in sheep following prenatal intra-amniotic injection of lipopolysaccharide.

Chorioamnionitis is an important problem in perinatology today, leading to brain injury and neurological handicaps. However, there are almost no data available regarding chorioamnionitis and a specific damage of the cerebellum. Therefore, this study aimed at determining if chorioamnionitis causes cerebellar morphological alterations. Chorioamnionitis was induced in sheep by the intra-amniotic injection of lipopolysaccharide (LPS) at a gestational age (GA) of 110 days. At a GA of 140 days, we assessed the mean total and layer-specific volume and the mean total granule cell (GCs) and Purkinje cell (PC) number in the cerebelli of LPS-exposed and control animals using high-precision design-based stereology. Astrogliosis was assessed in the gray and white matter (WM) using a glial fibrillary acidic protein staining combined with gray value image analysis. The present study showed an unchanged volume of the total cerebellum as well as the molecular layer, outer and inner granular cell layers (OGL and IGL, respectively), and WM. Interestingly, compared with controls, the LPS-exposed brains showed a statistically significant increase (+20.4%) in the mean total number of GCs, whereas the number of PCs did not show any difference between the two groups. In addition, LPS-exposed animals showed signs of astrogliosis specifically affecting the IGL. Intra-amniotic injection of LPS causes morphological changes in the cerebellum of fetal sheep still detectable at full-term birth. In this study, changes were restricted to the inner granule layer. These cerebellar changes might correspond to some of the motor or non-motor deficits seen in neonates from compromised pregnancies.

The lumbosacral angle does not reflect progressive tethered cord syndrome in children with spinal dysraphism.

PURPOSE: Our goal was to validate the hypothesis that the lumbosacral angle (LSA) increases in children with spinal dysraphism who present with progressive symptoms and signs of tethered cord syndrome (TCS), and if so, to determine for which different types and/or levels the LSA would be a valid indicator of progressive TCS. Moreover, we studied the influence of surgical untethering and eventual retethering on the LSA. METHODS: We retrospectively analyzed the data of 33 children with spinal dysraphism and 33 controls with medulloblastoma. We measured the LSA at different moments during follow-up and correlated this with progression in symptomatology. RESULTS: LSA measurements had an acceptable intra- and interobserver variability, however, some children with severe deformity of the caudal part of the spinal column, and for obvious reasons those with caudal regression syndrome were excluded. LSA measurements in children with spinal dysraphism were significantly different from the control group (mean LSA change, 21.0° and 3.1° respectively). However, both groups were not age-matched, and when dividing both groups into comparable age categories, we no longer observed a significant difference. Moreover, we did not observe a significant difference between 26 children with progressive TCS as opposed to seven children with stable TCS (mean LSA change, 20.6° and 22.4° respectively). CONCLUSIONS: We did not observe significant differences in LSA measurements for children with clinically progressive TCS as opposed to clinically stable TCS. Therefore, the LSA does not help the clinician to determine if there is significant spinal cord tethering, nor if surgical untethering is needed.

Polymorphisms in CACNA1E and Camk2d are associated with seizure susceptibility of Sprague-Dawley rats.

Seizures are associated with high intracellular calcium levels. However, conditions characterized by high intracellular calcium levels, such as stroke or traumatic brain injury, do not always evoke epilepsy. We hypothesized that polymorphisms in calcium-related genes CACNA1E and Camk2d contribute to the individual variability in seizure susceptibility. The distribution of one single nucleotide polymorphism (SNP) in the CACNA1E and one in the Camk2d gene was determined in Sprague-Dawley rats that were subjected to amygdala kindling or hyperthermia-induced seizures. The pre-kindling afterdischarge threshold was significantly lower in rats with the CACNA1E GG genotype (45.2+/-6.7microA) than in the GT genotyped animals (79.3+/-53.7microA). Among hyperthermia treated rats, the Camk2d G allele was more frequent among rats that did not display behavioral seizures during hyperthermia (67%) than in animals that did show behavioral seizures during hyperthermia (52%, chi(2)(1)=3.847, p=0.05). SNPs in CACNA1E and Camk2d genes are associated with the individual variability in seizure susceptibility in two experimental seizure models.

The clinical spectrum of Blake's pouch cyst: report of six illustrative cases.

INTRODUCTION: Although Blake's pouch cyst (BPC) is frequently mentioned in the spectrum of posterior fossa cysts and cystlike malformations since its first description in 1996, its natural history, clinical presentation, specific imaging characteristics, optimal treatment, and outcome are relatively unknown. Consequently, BPC may still be underdiagnosed. We therefore report six cases ranging from a fatal hydrocephalus in a young boy, over an increasing head circumference with or without impaired neurological development in two infants, to a decompensating hydrocephalus at an advanced age. DISCUSSION: We focus on their radiological uniformity, which should help making the correct diagnosis, and widely variable clinical presentation, which includes adult cases as well. Differentiating BPC from other posterior fossa cysts and cystlike malformations and recognizing the accompanying hydrocephalus are essentially noncommunicating, not only have important implications on clinical management but also on genetic counseling, which is unnecessary in case of BPC. In our experience, endoscopic third ventriculostomy is a safe and effective treatment option, avoiding the risks and added morbidity of open surgery, as well as many shunt-related problems.

Acute seizure-suppressing effect of vagus nerve stimulation in the amygdala kindled rat.

PURPOSE: Vagus nerve stimulation (VNS) is a moderately effective anti-epileptic treatment. Clinically relevant animal models that are suitable to study the mechanism of action of VNS are not available. The aim of the current study was to develop a clinically relevant animal model for VNS-treated epilepsy that can be used to study the mechanism of action of VNS. METHODS: The anticonvulsive effect of VNS was studied in fully kindled rats by measuring behavioral and electrophysiological parameters. Afferent vagus nerve activation was confirmed by quantifying nNOS immunoreactive cells in the nucleus of the solitary tract (NTS). RESULTS: VNS rats had more nNOS immunoreactive cells/mm(2) in the NTS than shams. VNS induced a >25% decrease in stage 5 duration (S5D) in 32% of rats. Prior to VNS this type of responders suffered from seizures with a longer total seizure duration (TSD) than non-responders. In 21% of rats VNS resulted in a >25% decrease in TSD. This type of responders had a shorter TSD prior to VNS than non-responders. In 29% of rats VNS resulted in >200% increase in stage 5 latency (S5L). This type of responders had higher kindling rates than non-responders. CONCLUSION: The VNS-treated kindled rat is a clinically relevant animal model because it is a chronic epilepsy model that responds to VNS with effects that are comparable to the effects of VNS in epilepsy patients. In addition, this study demonstrates that VNS-treated kindled rats can be used to study the mode of action of VNS using immunohistochemical techniques.

Intramedullary cavernoma presenting with hematomyelia: report of two girls.

INTRODUCTION: Less than 20 children with intramedullary cavernoma (ImC) have been reported in the English literature; however, cases with an unfavorable outcome may be underreported. Whereas these are predominantly boys, we report two girls who presented with hematomyelia (one cervical, one thoracic) and an acute, severe neurological deficit. CASE MATERIAL: A 10-year-old girl complaining about lower thoracic pain for several days suddenly developed lower body dysesthesias and paraparesis. Magnetic resonance (MR) demonstrated hematomyelia (T8-T11), intramedullary edema (T6-L1), and an ImC at T9-T10. Within an hour, she progressed to paraplegia and was therefore operated immediately. She slowly recovered regaining independent ambulation and continence. MR after 2 years shows no recurrence. A 7-year-old girl suddenly developed cervicalgia and paresis of her left arm and leg. MR demonstrated hematomyelia and an ImC at C4-C6. She gradually recovered with minimal residual deficit at 3 months and was subsequently operated uneventfully. Multiple cerebral cavernomas and a familial autosomal cavernous malformation syndrome were diagnosed. The following 1.5 years, she complained of intermittent cervicalgia and left brachial dysesthesias, with MR suggesting active residual cavernoma. Interestingly, her complaints gradually disappeared, and she is currently asymptomatic. MR after 3.5 years shows minimal cord swelling no longer suggesting active residual cavernoma. CONCLUSION: With adequate surgical treatment either in the acute phase in case of dramatic deterioration or after clinical recuperation, prognosis of symptomatic ImC may be surprisingly good. However, subtotally resected lesions and/or syndromal cases may recur, requiring further treatment. Definitive answers await more cases with longer follow-up.

[Babies with cranial deformity]. / Zuigelingen met een scheef hoofd.

Plagiocephaly was diagnosed in a baby aged 4 months and brachycephaly in a baby aged 5 months. Positional or deformational plagio- or brachycephaly is characterized by changes in shape and symmetry of the cranial vault. Treatment options are conservative and may include physiotherapy and helmet therapy. During the last two decades the incidence of positional plagiocephaly has increased in the Netherlands. This increase is due to the recommendation that babies be laid on their backs in order to reduce the risk of sudden infant death syndrome. We suggest the following: in cases of positional preference of the infant, referral to a physiotherapist is indicated. In cases of unacceptable deformity of the cranium at the age 5 months, moulding helmet therapy is a possible treatment option.

AChR deficiency due to epsilon-subunit mutations: two common mutations in the Netherlands.

Congenital myasthenic syndromes are a clinically and genetically heterogeneous group of hereditary disorders affecting neuromuscular transmission. We have identified mutations within the acetylcholine receptor (AChR) epsilon-subunit gene underlying congenital myasthenic syndromes in nine patients (seven kinships) of Dutch origin. Previously reported mutations epsilon1369delG and epsilonR311Q were found to be common; epsilon1369delG was present on at least one allele in seven of the nine patients, and epsilonR311Q in six. Phenotypes ranged from relatively mild ptosis and external ophthalmoplegia to generalized myasthenia. The common occurrence of epsilonR311Q and epsilon1369delG suggests a possible founder for each of these mutations originating in North Western Europe, possibly in Holland. Knowledge of the ethnic or geographic origin within Europe of AChR deficiency patients can help in targeting genetic screening and it may be possible to provide a rapid genetic diagnosis for patients of Dutch origin by screening first for epsilonR311Q and epsilon1369delG.

Nitrotyrosine in human neonatal spinal cord after perinatal asphyxia.

BACKGROUND: Spinal cord injury has been reported after perinatal asphyxia in full-term neonates. OBJECTIVES: To examine the role of excessive nitric oxide production in perinatal spinal cord injury. SUBJECTS AND METHODS: Tissue samples of 18 full-term neonates who died of hypoxic-ischemic encephalopathy were analyzed for the presence of nitrotyrosine (NT). RESULTS: NT was demonstrated in 5 of these 18 neonates. In addition, activated caspase 3, a marker of apoptosis, and CD68, as a marker of inflammation, could be demonstrated in some infants. CONCLUSIONS: excessive nitric oxide production and subsequent NT formation is seen in spinal cord tissue after severe perinatal asphyxia. This finding may be relevant for the development of neuroprotective strategies.

The Currarino triad: neurosurgical considerations.

OBJECTIVES: The Currarino triad, a relatively uncommon hereditary disorder, is often associated with tethered cord and anterior myelomeningocele. Little is known of the implications of these neuroanatomic malformations or of the neurosurgical attitude. The objective of this study is to identify the spinal cord and meningeal malformations associated with the Currarino triad and to discuss the risks and benefits of surgical intervention. METHODS: We analyzed the spinal cord malformations and the neurosurgical involvement with the Currarino triad by retrospective chart review. RESULTS: The Currarino triad neuroanatomic malformations were identified in five patients. The Currarino triad was associated with a tethered cord in three patients, a myelomeningocele in five patients, a syrinx in two patients, a fistula between the colon and spinal canal in two patients, and an Arnold-Chiari Type 1 malformation in one patient. CONCLUSION: Full spine imaging is required for all patients diagnosed with the Currarino triad. Magnetic resonance imaging of the head should be performed in every patient with neuroanatomic anomalies. Surgery of an anterior myelomeningocele is not necessarily indicated, only in the rare case in which the space-occupying aspect is expected to cause constipation or problems during pregnancy or delivery. Constipation directly after birth is seen in virtually all patients with the triad. Therefore, constipation cannot be used to diagnose a tethered cord syndrome nor indicate tethered cord release. Fistulas between the spinal canal and colon have to be operated on directly.