Deborah A. Sival

Does fetal endoscopic closure of the myelomeningocele prevent loss of neurologic function in spina bifida aperta

Background Spina bifida aperta (SBA) is associated with shuntdependent hydrocephalus and with meningomyelocele (MMC). Fetal endoscopic closure of the MMC may reduce shunt-dependency, but the benefit upon motor function in individual patients is still unclear. An increase in differentiated muscle ultrasound density (dMUD) provides an objective parameter for the extent of muscle damage caudal to the MMC. In this perspective, we aimed to compare dMUD and neurological function between SBA children treated by fetal endoscopic closure (fSBA) and by neonatal closure (nSBA) of the MMC.

Fetal endoscopic myelomeningocele closure preserves segmental neurological function

Aim  Our aim was to compare the effect of prenatal endoscopic with postnatal myelomeningocele closure (fetally operated spina bifida aperta [fSBA]) versus neonatally operated spina bifida aperta [nSBA]) on segmental neurological leg condition.

Neuroependymal Denudation is in Progress in Full-term Human Foetal Spina Bifida Aperta

In human spina bifida aperta (SBA), cerebral pathogenesis [hydrocephalus, Sylvius aqueduct (SA) stenosis and heterotopias] is poorly understood. In animal models, loss of ventricular lining (ependymal denudation) causes SA stenosis and hydrocephalus. We aimed to investigate whether ependymal denudation also takes place in human foetal SBA. Considering that ependymal denudation would be related to alterations in junction proteins, sections through SA of five SBA and six control foetuses (gestational ages ranged between 37 and 40 weeks) were immunostained for markers of ependyma (caveolin 1, βIV‐tubulin, S100), junction proteins (N‐cadherin, connexin‐43, neural cell adhesion molecule (NCAM), blood vessels (Glut‐1) and astrocytes [glial fibrillary acidic protein (GFAP)]. In control foetuses, ependymal denudation was absent. In SBA foetuses different stages of ependymal denudation were observed: (i) intact ependyma/neuroepithelium; (ii) imminent ependymal denudation (with abnormal subcellular location of junction proteins); (iii) ependymal denudation (with protrusion of neuropile into SA, formation of rosettes and macrophage invasion); (iv) astroglial reaction. It is suggested that abnormalities in the formation of gap and adherent junctions result in defective ependymal coupling, desynchronized ciliary beating and ependymal denudation, leading to hydrocephalus. The presence of various stages of ependymal denudation within the same full‐term SBA foetuses suggests continuation of the process after birth.

Long-term outcome in pyridoxine-dependent epilepsy.

Aim  The long‐term outcome of the Dutch pyridoxine‐dependent epilepsy cohort and correlations between patient characteristics and follow‐up data were retrospectively studied.

Ataxia rating scales are age‐dependent in healthy children

To investigate ataxia rating scales in children for reliability and the effect of age and sex.

The EEG response to pyridoxine-IV neither identifies nor excludes pyridoxine-dependent epilepsy

Purpose:  Pyridoxine‐dependent epilepsy (PDE) is characterized by therapy‐resistant seizures (TRS) responding to intravenous (IV) pyridoxine. PDE can be identified by increased urinary alpha‐aminoadipic semialdehyde (α‐AASA) concentrations and mutations in the ALDH7A1 (antiquitin) gene. Prompt recognition of PDE is important for treatment and prognosis of seizures. We aimed to determine whether immediate electroencephalography (EEG) alterations by pyridoxine‐IV can identify PDE in neonates with TRS.

Favorable Outcome in a Newborn With Molybdenum Cofactor Type A Deficiency Treated With cPMP

Molybdenum cofactor deficiency (MoCD) is a lethal autosomal recessive inborn error of metabolism with devastating neurologic manifestations. Currently, experimental treatment with cyclic pyranopterin monophosphate (cPMP) is available for patients with MoCD type A caused by a mutation in the MOCS-1 gene. Here we report the first case of an infant, prenatally diagnosed with MoCD type A, whom we started on treatment with cPMP 4 hours after birth. The most reliable method to evaluate neurologic functioning in early infancy is to assess the quality of general movements (GMs) and fidgety movements (FMs). After a brief period of seizures and cramped-synchronized GMs on the first day, our patient showed no further clinical signs of neurologic deterioration. Her quality of GMs was normal by the end of the first week. Rapid improvement of GM quality together with normal FMs at 3 months is highly predictive of normal neurologic outcome. We demonstrated that a daily cPMP dose of even 80 μg/kg in the first 12 days reduced the effects of neurodegenerative damage even when seizures and cramped-synchronized GMs were already present. We strongly recommend starting cPMP treatment as soon as possible after birth in infants diagnosed with MoCD type A.

Dystonia in children and adolescents: a systematic review and a new diagnostic algorithm

Early aetiological diagnosis is of paramount importance for childhood dystonia because some of the possible underlying conditions are treatable. Numerous genetic and non-genetic causes have been reported, and diagnostic workup is often challenging, time consuming and costly. Recently, a paradigm shift has occurred in molecular genetic diagnostics, with next-generation sequencing techniques now allowing us to analyse hundreds of genes simultaneously. To ensure that patients benefit from these new techniques, adaptation of current diagnostic strategies is needed. On the basis of a systematic literature review of dystonia with onset in childhood or adolescence, we propose a novel diagnostic strategy with the aim of helping clinicians determine which patients may benefit by applying these new genetic techniques and which patients first require other investigations. We also provide an up-to-date list of candidate genes for a dystonia gene panel, based on a detailed literature search up to 20 October 2014. While new genetic techniques are certainly not a panacea, possible advantages of our proposed strategy include earlier diagnosis and avoidance of unnecessary investigations. It will therefore shorten the time of uncertainty for patients and their families awaiting a definite diagnosis.

Intraspinal dermoid and epidermoid tumors: report of 18 cases and reappraisal of the literature.

Intraspinal dermoid and epidermoid tumors are two histopathological subtypes of cutaneous inclusion tumors of the spine. This classification is based on obsolete embryological knowledge. In fact, according to current embryology, both tumor types consist of ectodermal derivatives. Therefore, we hypothesized that dermoid and epidermoid tumors do not differ in clinical practice. To explore this hypothesis, we studied the clinical, radiological and intraoperative findings of 18 patients, and related these findings to the histopathological characteristics of the tumor. No differences were found between dermoid and epidermoid tumors regarding clinical presentation, radiological examination and outcome, while intraoperative diagnosis by the surgeon correlated with the histopathological diagnosis in only 8 of 18 cases. Therefore, the histopathological difference between intraspinal dermoid and epidermoid tumors is not important in clinical practice and should be avoided. A new nomenclature is proposed in which both tumor types are referred to as ‘spinal cutaneous inclusion tumors’.

Ramsay Hunt Syndrome: Clinical Characterization of Progressive Myoclonus Ataxia Caused by GOSR2 Mutation

Ramsay Hunt syndrome (progressive myoclonus ataxia) is a descriptive diagnosis characterized by myoclonus, ataxia, and infrequent seizures. Often the etiology cannot be determined. Recently, a mutation in the GOSR2 gene (c.430G>T, p.Gly144Trp) was reported in 6 patients with childhood‐onset progressive ataxia and myoclonus.