Newborns with myelomeningocele: their health-related quality of life and daily functioning 10 years later.

OBJECTIVE: Ten years ago, the authors reported on the outcome of their study investigating the degree of discomfort and pain in newborns with myelomeningocele (MMC), using the parameters of unbearable and hopeless suffering. In the current study, they investigated the quality of life, daily functioning, pain and fatigue, ability to communicate, and number of surgeries in the same cohort of patients. They subdivided their study population into severe (Lorber) and less severe (non-Lorber) cases and compared these cases with a healthy population (non-MMC group) and with each other. METHODS: The parents of 22 of 28 patients gave informed consent for this study. The KIDSCREEN-27 and PEDI-CAT (Pediatric Evaluation of Disability Inventory) were used to assess quality of life and daily functioning. Pain and fatigue were self-reported on a 10-point numeric rating scale. Communication and ambulation levels were determined using the Communication Function Classification System (CFCS) and the Hoffer ambulation scale. Using reference data from the KIDSCREEN-27 and PEDI-CAT, the authors created a healthy population comparison group. RESULTS: There was no significant difference in health-related quality-of-life (HRQOL) scores between Lorber and non-Lorber patients, except that school environment domain scores were lower in the Lorber group. When comparing the HRQOL of MMC patients with that of the non-MMC group, the physical well-being and parent relations and autonomy domains scored significantly lower. The daily functioning of MMC patients was lower on all domains of the PEDI-CAT compared with the non-MMC group. Lorber MMC patients scored lower on all domains of the PEDI-CAT when compared with non-Lorber patients. All patients were capable of communicating effectively; most patients (n = 18) were considered CFCS level I, and 4 patients were considered CFCS level II. CONCLUSIONS: This study shows that MMC is a severe, lifelong condition that affects patients' lives in many domains. All the patients in this study are capable of effective communication, irrespective of severity of MMC. Overall, the data show that in newborn MMC patients, future unbearable suffering with respect to pain, mobility, cognition, and communication is hard to predict and may not always occur.

[To act or not to act? Developments in prenatal and postnatal care for children with spina bifida aperta]. / Handelen of niet handelen?

To act or not to act? Developments in prenatal and postnatal care for children with spina bifida aperta Until the middle of the twentieth century, newborns with spina bifida aperta had low chances of survival. Advances in the treatment of hydrocephalus, among other conditions, led to increased chances of survival during the 1960s. This also revealed the downsides of the treatment of spina bifida patients since some considered the quality of life of a number of these patients to be unacceptable. But withholding treatment also had negative consequences, leading to an ethical deadlock. Over the past thirty years - besides postnatal closure of the neural tube defect - more emphasis has been put on selective pregnancy termination and sporadic active termination of life in newborns with very severe forms of spina bifida. At the same time, new treatment strategies, such as foetal surgery, are being developed. With this historical overview, we illustrate the way in which technological developments and ethical dilemmas are constantly affecting each other.

Motor performance and functional mobility in children with specific learning disabilities.

INTRODUCTION: Limitations in motor performances among children with specific learning disabilities (SLD) can lead to impaired functional skills. Thus, this study aimed to determine the level of motor performances and functional mobility, and the influence of motor performances on the functional mobility in children with SLD. METHODS: A cross-sectional study was conducted among 148 children with SLD and their caregivers. The evaluation consisted of the Movement Assessment Battery for Children-2 (MABC-2) and the Functional Mobility domain from Pediatric Evaluation of Disability Inventory-Computer Adaptive Test (PEDI-CAT). The level of motor performances and functional mobility were determined. A linear regression was then conducted to assess the influence of motor performances that could be accounted for functional mobility scores. RESULTS: More than half of the children with SLD showed motor performance difficulty in manual dexterity subscale (54.7%). For functional mobility, the mean standard T-score indicated an average level of capability (49.49±15.96). A regression analysis revealed that both manual dexterity and balance were significant predictors for functional mobility. According to the regression coefficients, manual dexterity (B=1.37, ß=0.303, sr2=0.077) was found to be a stronger predictor compared to balance (B=0.85, ß=0.178, sr2=0.028). CONCLUSION: Manual dexterity was found to influence functional mobility among children with SLD. Therefore, fine motor skills intervention for children with SLD should emphasize on manual dexterity training. Future studies that involve dual tasks and inclusion of typical children would give useful additional information on motor performances issues in children with SLD.

Minimally Invasive, Spring-Assisted Correction of Sagittal Suture Synostosis: Technique, Outcome, and Complications in 83 Cases.

BACKGROUND: This series describes the results of minimally invasive strip craniotomy with additional spring distraction. METHODS: Included are the first 83 consecutive patients who underwent this procedure (January 1, 2010, to January 1, 2014). Outcome parameters were collected prospectively and included surgical parameters and complications, the occurrence of papilledema, skull growth, cephalic index, and photographic scores. RESULTS: Duration of surgery was 63 minutes, 19 percent required blood transfusion, and complications were minor. Postoperative papilledema occurred in two patients (2.4 percent). Head growth increased after insertion of the springs and declined afterward to 0.7 SD, comparable to earlier cohorts in the authors' center. The cephalic index increased from 67 before surgery to 74 after surgery and showed a small decrease during the 4-year follow-up. Photographic scores confirmed the initial improvement and showed a trend to further improvement during follow-up. CONCLUSIONS: In this cohort, spring-assisted, minimally invasive strip craniotomy was safe and effective. Results were similar to those from other techniques but with smaller incisions, shorter interventions, reduced blood loss, and a lower incidence of postoperative papilledema. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Screening and Treatment of Tethered Spinal Cord in Anorectal Malformation Patients.

INTRODUCTION: This study aims to evaluate diagnosis and treatment of tethered spinal cord (TSC) in anorectal malformation (ARM) patients. MATERIAL AND METHODS: A retrospective case study was performed on patients with an ARM born between 2004 and 2011 and treated at the Erasmus MC-Sophia Children's Hospital. RESULTS: During the study period, 110 neonates with ARM were treated. Spinal ultrasonography was performed in 94 (85%) patients. Ultrasonography findings were abnormal in 17 patients (18%): 16 had evidence for TSC and 1 for caudal regression. These findings were confirmed by magnetic resonance imaging (MRI) in eight patients. Six of the other 76 patients developed neurologic symptoms and MRI revealed evidence for TSC in 2 of those 6 patients. Thus, sensitivity of spinal ultrasonography was 80%, specificity was 89%, the positive predictive value was 47%, and the negative predictive value was 97%. The prevalence of TSC, as confirmed by MRI, was 9%. Three patients underwent untethering surgery: one patient developed neurologic symptoms and two patients were asymptomatic at the time of surgery (MRI showed progressive syringomyelia in one and the other had a dermal sinus with TSC). All operations were without any complications and the symptoms resolved in the first patient. A relationship between TSC and a specific type of ARM or syndrome disorder could not be found. CONCLUSIONS: Tethered cord occurs in 9% of the ARM patients. Neonatal spinal ultrasonography has a sensitivity and specificity of 80 and 89%, respectively. Not in all patients an MRI was performed, but the vast majority remained clinically asymptomatic concerning TSC. Ultrasound screening seems an effective screening method, however, when ultrasonography is negative and the patient becomes symptomatic later in life, an MRI should be performed to exclude TSC. In our series, only 1 of 110 ARM patients had symptomatic tethered cord syndrome, and symptoms resolved postoperatively.

Endoscopic third ventriculocisternostomy in hydrocephalic children under 2 years of age: appropriate or not? A single-center retrospective cohort study.

PURPOSE: Treating hydrocephalus can be difficult in children under the age of 2 years because a high amount of uncertainty exists as to which treatment to perform. In this retrospective cohort study, we analyzed children under the age of 2 years with hydrocephalus undergoing an endoscopic third ventriculocisternostomy (ETV) with respect to ETV outcome. METHODS: In 59 consecutive patients under the age of 2 years, an ETV was performed between 1999 and 2010 at the Erasmus MC, Sophia Children's Hospital. Demographics, etiology of hydrocephalus, and radiological data were extracted retrospectively from the patients' medical records and operative reports and related to outcome. ETV Success Score (ETVSS) was used to retrospectively calculate the probability of success related to the actual outcome. RESULTS: In this series, 42.4 % of patients had a successful ETV. The only statistically significant finding concerned age. The failed ETV patients appeared to be younger (0.52 ± 0.60 vs. 0.86 ± 0.56 year, p = 0.005), and when using a cutoff age of 6 months only, five out of 32 infants had a successful ETV (p = 0.002). Of the children with an arachnoid cyst, 57.1 % were treated successfully with an ETV. Of the five patients with a high probability of ETV success, four (80 %) were indeed successfully treated with ETV (p = 0.049). CONCLUSIONS: Our data confirm the overall ineffectiveness of an ETV in children under the age of 6 months. Nevertheless, using the ETVSS is recommended to aid in the decision-making process even in patients under the age of 6 months.

Discomfort and pain in newborns with myelomeningocele: a prospective evaluation.

OBJECTIVE: In a worldwide debate on deliberately terminating the lives of newborns, proponents point at newborns with very severe forms of myelomeningocele (MMC) and their assumed suffering, claiming there are no effective means of alleviating their distress. Nevertheless, the degree of discomfort and pain in these newborns has never been assessed in a structured manner. METHODS: In a prospective cohort study, 28 consecutive newborns with MMC were included over a 5-year period and were followed up throughout their hospital stay for initial treatment. We created 2 disease severity groups on the basis of the Lorber criteria. The primary outcomes were discomfort and pain, assessed by simultaneously scoring 2 validated scales: the visual analog scale for pain and the Comfort Behavioral Scale for discomfort. These scores were coupled to a validated and evidence-based analgesia algorithm. RESULTS: Overall, discomfort related to pain was measured in 3.3% of the scores. This percentage differed little between the preoperative and postoperative periods and did not significantly differ between newborns with less severe MMC and severe MMC (3.9% vs 2.8%; P = .3). The mean dosage of paracetamol was 35 mg/kg per day (95% confidence interval: 32-39); the mean dosage of morphine was 0.9 µg/kg per hour (95% confidence interval: 0.6 -1.2). CONCLUSION: Over the length of their hospital stays for initial treatment, all newborns with MMC presented with low levels of discomfort and pain independent of disease severity and time frame.

The interplay between Eps8 and IRSp53 contributes to Src-mediated transformation.

As an oncoprotein, Eps8 participates in v-Src-induced cellular transformation. To delineate the underlying mechanism, we conducted a yeast two-hybrid screening and identified IRSp53S, a protein critical in cell mobilization, as one of the Eps8-binding partners from a human brain cDNA library. The association was mediated by the multiple proline-rich regions of Eps8 and the C-terminal SH3-WWB containing domains of IRSp53S. In this study, we observed that Eps8 modulated the expression of IRSp53 in v-Src-transformed cells (IV5), raising the question of whether Eps8/IRSp53 interaction was crucial in carcinogenesis. To address this issue, we generated IV5-expressing irsp53 siRNA cells. Attenuation of IRSp53 reduced cell proliferation of IV5 in culture dish and tumor formation in mice, which could be partly rescued by ectopically expressed human IRSp53S. In addition, IRSp53 knockdown impaired activity of phosphatidylinositol 3-kinase (as reflected by Pi-Ser473 AKT) and Stat3 (as reflected by Pi-Tyr705 Stat3), and reduced cyclin D1 expression that culminated to impede G(1)-phase cell-cycle progression. Ectopically expressed human IRSp53S, but not its Eps8-binding defective mutants (that is, Delta363 and PPPDA), rescued these defects and partly restored cell proliferation. Remarkably, through activation of Src, EGF increased the formation of Eps8/IRSp53 complex and Stat3 activation in HeLa cells. With these results, we show for the first time that IRSp53, through its interaction with Eps8, not only affects cell migration but also dictates cellular growth in cancer cells.

Deliberate termination of life of newborns with spina bifida, a critical reappraisal.

OBJECTS: Deliberate termination of life of newborns (involuntary euthanasia) with meningomyelocele (MMC) is practiced openly only in The Netherlands. 'Unbearable and hopeless suffering' is the single most cited criterion for this termination, together with the notion that 'there are no other proper medical means to alleviate this suffering'. In this paper, both (and other) statements are questioned, also by putting them in a broader perspective. METHODS: First, a historical overview of the treatment of newborns with MMC is presented, concentrating on the question of selection for treatment. Second, a thorough analysis is made of the criteria used for life termination. Third, a case of a newborn with a very severe MMC is presented as a 'reference case'. CONCLUSION: 'Unbearable and hopeless suffering' cannot be applied to newborns with MMC. They are not 'terminally ill' and do have 'prospects of a future'. In these end-of-life decisions, 'quality of life judgments' should not be applied. When such a newborn is not treated, modern palliative care always will suffice in eliminating possible discomfort. There is no reason whatsoever for active life-termination of these newborns.

Primitive neuroectodermal tumours (PNETs) located in the spinal canal; the relevance of classification as central or peripheral PNET : case report of a primary spinal PNET occurrence with a critical literature review.

Intraspinal location of central PNET (cPNET) is very rare. We present a case, critically review all publications of primary intraspinal cPNET occurrence and discuss tendencies in clinical presentation. In several previous attempts to summarise, authors often confused cPNET with peripheral PNET (pPNET). cPNET and pPNET are different entities with different immunohistochemical profiles and genetic backgrounds. Clinically, they are both aggressive tumours, but exhibit different characteristics in their local manifestation and metastatic spread. Survival rates are quite similar provided that treatment is applied according to the established protocols. Protocols in cPNET treatment differ from those for pPNET as regards the order of the treatment sub-modalities, specific chemotherapeutic regimen and intensity, radiation dose and its extent and consequently, the side effects. Therefore, failure to distinguish cPNET from pPNET leads to clinical guidance and treatment proposals based on false assumptions, which might effect outcomes. Often, distinguishing between cPNET and pPNET is easy, because they occur in different location. In the case of intraspinal tumour location, however, the differentiation is crucial because both primary cPNET and pPNET can occur intraspinally, even though this is rare. Nowadays, demonstrating the expression of MIC2 glycoprotein by immunocytochemical staining (CD99) showing the specific EWS-FLI1 chimeric gene presence in pPNET, offers an easy way of making a differential diagnosis between cPNET and pPNET.

[Questionable basis for 'hopeless and unbearable suffering' as the criterion for the active termination of life in newborns with spina bifida]. / Problematische basis voor 'uitzichtloos en ondraaglijk lijden' als criterium voor actieve levensbeëindiging bij pasgeborenen met spina bifida.

Is 'hopeless and unbearable suffering' a just criterion for the deliberate termination of life of newborns with spina bifida? Hopeless suffering, with no means of alleviation, is not applicable in the acute phase of spina bifida in newborns, but to the chronic suffering that comes later on as the result of pain and discomfort experienced by the patient. There is a need for a nationwide discussion on (a) how can we determine when acute or chronic suffering become hopeless and unbearable, and on what basis should a given situation be regarded as an 'emergency situation'?; (b) what qualifies as a very severe form of spina bifida?; (c) what kind of care should be provided after the decision to withhold active care?

Visual loss in syndromic craniosynostosis with papilledema but without other symptoms of intracranial hypertension.

Four children with syndromic craniosynostosis (Crouzon's syndrome and Apert syndrome) developed irreversible visual loss. Apart from papilledema, there were no other clinical symptoms of intracranial hypertension. Ventriculomegaly or hydrocephalus was present in all cases. Two children were known to have obstructive sleep apnea syndrome. These cases are reported to inform specialists involved in follow-up of children with syndromic craniosynostosis that visual loss can develop suddenly without other symptoms of intracranial hypertension. To prevent visual loss, papilledema should be detected at an early stage and intervention should be instituted promptly. Therefore, periodic funduscopy should be performed in children at risk, such as children with syndromic craniosynostosis and additional hydrocephalus or obstructive sleep apnea syndrome.

Thoracic meningocele, meningomyelocele or myelocystocele? Diagnostic difficulties, consequent implications and treatment.

Spina bifida cystica is a closing disorder of the neural tube which infrequently occurs in the thoracic region. A rare lesion called myelocystocele is a variant of spina bifida cystica and is associated with syringomyelia, Chiari type 2 malformation and hydrocephalus. Usually the patient has no neurological deficit, but future deterioration can occur due to posterior tethering of the spinal cord by adhesions. The prenatal diagnosis by ultrasound study can be misleading and in order to attain the correct diagnosis, especially if abortion is considered, a prenatal MRI scan should be done before the parents are counselled, and should be repeated prior to operative treatment. Surgical correction of myelocystocele is not only for cosmetic reasons, but also to untether the spinal cord prophylactically to prevent future neurological deterioration. In this case report, we present a child born with a thoracic myelocystocele, the diagnostic difficulties, consequent implications and surgical treatment.

Acetaminophen in cerebrospinal fluid in children.

BACKGROUND: There are few studies describing acetaminophen (APAP) cerebrospinal fluid (CSF) concentrations in children. This current study was undertaken in children--from neonates to adolescents--in order to investigate age-related changes in the plasma to CSF equilibration half-time (Teq) of APAP. METHODS: Children (n=41) 1 week to 18 years of age undergoing (semi) elective surgery for placement or revision of a ventriculo-peritoneal shunt or insertion of a temporary external ventricular drain received a loading dose of 30-40 mg/kg APAP 1 h before scheduled surgery. Blood and CSF samples for APAP concentration analysis were collected during surgery. In those children with a temporary external drain, blood and CSF sampling were extended into the postoperative period. APAP and CSF pharmacokinetics were estimated using non-linear mixed-effects models. Size was standardized to a 70-kg person using allometric "1/4 power models". RESULTS: Median (25-75th percentile) age and weight of the patients included in this study were 12 months (3-62 months) and 10.0 kg (5.8-20.0 kg). Median (25-75th percentile) time between APAP loading dose administration and collection of blood samples and median time (25-75th percentile) between APAP loading dose and collection of CSF were, respectively, 125 min (95-210 min) and 133 min (33-202 min). The population mean Teq, standardized to a 70-kg person, was 1.93 h (CV 43%), an estimate similar to that described in adults (2.1 h). There was no relationship between age and Teq other than that predicted by size. APAP plasma concentrations ranged from 0.0 mg/l to 33.0 mg/l, APAP CSF concentrations ranged from 0.0 mg/l to 21.0 mg/l. CONCLUSION: Size rather than blood-brain-barrier maturation determines Teq changes with age in children. We predict a neonate (3.5 kg), 1-year-old child (10 kg), 5-year-old child (20 kg), 10-year-old child (30 kg) and adult (70 kg) to have Teq values of 0.9, 1, 1.4, 1.6, and 1.93 h, respectively.

Desmoplastic infantile astrocytoma and ganglioglioma: a search for genomic characteristics.

In the present study the clinical data, histology, proliferation rate, DNA ploidy status and the results of TP53 mutation analysis and comparative genomic hybridization (CGH) of three typical cases of desmoplastic infantile astrocytoma and ganglioglioma are presented. Postoperative disease-free intervals of 11, 8 and 3 years were recorded and in none of the cases were radiological signs of tumor recurrence. No TP53 mutations (exons 5-8) were found. CGH analysis revealed loss of 8p22-pter in one case, while in another case gain of 13q21 was detected. In the case with the follow-up of 11 years an aneuploid DNA-flow cytogram along with slightly increased MIB-1 labeling index (LI) was found. The results demonstrate little genetic instability in these low-grade lesions. DNA-aneuploidy seems not to be indicative of tumor progression. It is concluded that the genetic aberrations found in desmoplastic infantile ganglioglioma differ from those encountered in common astrocytomas.

Tracing craniosynostosis to its developmental stage through bone center displacement.

In metopic and coronal suture synostosis, the involved bone centers are abnormally situated just next to the affected suture. Bone centers are the starting point of ossification during embryogenesis from which bone growth spreads radially. In this paper, we describe a similar observation for sagittal suture synostosis, with both parietal bone centers located almost completely cranially. The (reduced) distance between the bone centers of a synostotic suture reflects the time during embryogenesis at which fusion took place. We suggest that in craniosynostosis the bone centers arise in their normal position, and initial outgrowth is undisturbed until the bone fronts meet. It is during this developmental stage that fusion occurs instead of suture formation. Due to the fusion, growth can only occur at the free bony rims from then on. The bone centers remain located at a fixed distance from one another in the middle of the fused bones, becoming relatively more displaced with time. This implies that the distance between the involved bone centers directly indicates the developmental period during which sutural growth was arrested. The same phenomenon of bone center displacement is found in types of craniosynostosis with and without fibroblast growth factor receptor (FGFR) or TWIST gene mutations.

A giant cell tumor of the sacrum or a soft tissue giant cell tumor? A case report.

STUDY DESIGN: A case report. OBJECTIVE: Giant cell tumors are rare primary bone tumors. Generally, these tumors are expanding osteolytic lesions, but soft tissue giant cell tumors can occur. This is a case report of an unusual incidence of a giant cell tumor within the spinal sacral canal, in which there was no involvement of the surrounding bone or ligament structures and that was signaled by radicular pain. The pathologic course of the tumor is described. SUMMARY OF BACKGROUND DATA: A 24-year-old woman had monoradicular pain in the right leg in the region of S2. Neuroradiologic examination showed a mass within the sacral spinal canal compromising the right S2 root, with no sign of bone involvement. METHODS: A sacral laminectomy was performed. A tumor was located entirely intraspinally and extradurally and was removed completely. A giant cell tumor was identified in histologic examination. RESULT: The patient recovered completely. No local regrowth or metastasis occurred during a 20-month follow-up. CONCLUSION: The treatment of choice in giant cell tumors is complete surgical resection. Radiotherapy is recommended in cases of subtotal resection. Careful follow-up is warranted, because recurrence and metastasis are not uncommon.

Rapid evolution of a growing skull fracture after vacuum extraction in case of fetal hydrocephalus.

Vacuum extraction in nonprogressive labor is relatively safe. Only a few major complications have been mentioned. This article describes the rapid development of a growing skull fracture associated with a porencephalic cyst and parenchymal brain damage after a difficult vacuum extraction in a patient with congenital hydrocephalus and a thoracic meningomyelocele. The diagnostic and therapeutic management is discussed.

['Cerebral running nose': cerebrospinal rhinorrhea]. / 'Cerebrale loopneus': rhinorrhoea cerebrospinalis.

Cerebrospinal fluid rhinorrhoea was diagnosed in two patients, a man of 19 and a woman of 45 years old. This is a relatively rare phenomenon and clinically often difficult to differentiate from nasal secretions caused by a rhinopathy. Although cerebrospinal fluid (CSF) fistulae usually are of traumatic origin as in the first patient, they can also be caused by a congenital malformation as in the second one or by a condition with chronic increased intracranial pressure. With adequate treatment the prognosis is good. CSF can be identified very specifically by beta-transferrin determination.