Congenital Aqueductal Stenosis Research Articles

Endoscopic third ventriculostomy for obstructive hydrocephalus in children younger than 6 months of age: is it a first-choice method?

Endoscopic third ventriculostomy (ETV) is considered a safe procedure and is a method of choice in treatment of obstructive hydrocephalus nowadays. In case of Sylvian aqueduct stenosis, the success rate reaches 90%. In children younger than 6 to 24 months, respectively, however, some authors report lower effectiveness ranging between 0% and 64%. The reasons of ETV failure are discussed: hyporesorption in patients with obstruction as a consequence of hemorrhage or infection, suboptimal ETV performance, especially in premature newborns, or the theory of different cerebrospinal fluid circulation in newborn babies. Between January 2005 and December 2006 in our clinic, 14 patients younger than 6 months having presented with obstructive hydrocephalus were treated endoscopically. Obstruction was revealed by preoperative magnetic resonance imaging. The etiology of hydrocephalus was congenital aqueduct stenosis in five patients, posthemorrhagic obstruction in eight patients, and combination of posthemorrhagic and postinfection etiology in one patient. ETV was considered successful when no shunt operation was needed in the patient. ETV was successful in eight patients who experienced regression of signs of intracranial hypertension and were not forced to undergo ventriculo-peritoneal (V-P) shunting. In one patient, a successful repeat ETV was performed. In the remaining six patients, V-P shunt implantation was necessary. Total success rate in our group of patients was 57%. The only complication was subdural hygroma in one patient requiring evacuation. Based on our experience, we recommend ETV as the method of choice in children younger than 6 month of age.

Congenital aqueductal stenosis due to downregulation of a dorsalizing gene

Congenital aqueductal stenosis is a frequent cause of fetal hydrocephalus. We studied 9 human fetuses at midgestation with aqueductal stenosis for clues to etiology. Two had holoprosencephaly. Associated dysgeneses in all 9 included hypoplasia or agenesis of the corpus callosum; hippocampal and cerebellar dysplasias; absence of the dorsal median septum, confirmed by vimentin. The sagittal intercollicular fissure was absent or shallow with collicular continuity across the midline. In 2 cases, only the rostral mesencephalon was involved. These findings suggest downregulation of a gene acting in the dorsoventral gradient of the vertical axis of the neural tube, and also in rostrocaudal and mediolateral gradients.

Bilateral Chronic Subdural Haematoma After Endoscopic Third Ventriculostomy: Case Report and Review of the Literature

Several complications related to Endoscopic third ventriculostomy (ETV) have been reported in the literature including chronic subdural haematoma. This is usually unilateral. We report a case of a 12-month-old female child with bilateral chronic subdural haematoma (CSH) 3months after an ETV. She had a ventriculoperitoneal shunt at 5months of age on account of congenital aqueductal stenosis with marked cerebral mantle thining. At 9months of age an ETV was done due to shunt obstruction. The CSH was successfully treated by burr-hole evacuation on both sides. Though ETV is a simple, effective and safe procedure, and also the main stay of treatment for noncommunicating hydrocephalus in many centres, long term follow up should still be emphasised.

Mechanical Block of Shunt Chamber Due to Fungal Growth in an Immunocompetent Child

Invasive aspergillosis is a serious fungal infection caused by the proliferation and invasion of Aspergillus hyphae in tissue.1 Invasive aspergillosis is an increasing problem in immunocompetent patients after prolonged steroid therapy, cancer radiochemotherapy, and bone marrow or solid organ transplantation.2,3 Fungal ventriculoperitoneal shunt infections seem to be a complication of shunts placed in previously infected persons rather than nosocomial transmission during placement.4 We report a successfully treated case of shunt malfunction caused by mechanical block due to fungal growth inside the chamber in an immunocompetent child without systemic manifestations caused by Aspergillus fumigatus. CASE REPORT An 8-month-old female child with a case of congenital aqueductal stenosis with obstructive hydrocephalus underwent right ventriculoperitoneal shunt. Two months after surgery, she was apparently all right; then, again, she started to develop an increase in the size of her head. There was no history of fever and vomiting, and the child was playful and accepting feeds. On examination, anterior fontanelle was tense, and head circumference was 52 cm. Shunt tap was tried, but there was no flow of cerebrospinal fluid (CSF). The child was planned for shunt revision. During the procedure, the lower end was opened, but there was no flow of CSF even after pressing the chamber. After that, the upper end was opened; there was some whitish material in the chamber, and it was blocking the flow of CSF (Fig. 1). It was thought that it might be because of the collection of proteinaceous material. The material collected from the shunt tube and chamber was removed. Histopathology of whitish material collected from the shunt system showed fungal hyphae; after culture, there was growth of A.fumigatus (Figs. 2 and 3). These A. fumigatus isolates were identified by their cultural characteristics, their ability to grow at a temperature of 48°C, and the appearances of their conidiophores and conidia. Shunt tube was removed, and ventricular CSF was sent for fungal and bacterial culture and sensitivity. Ventricular CSF was sterile for both bacterial and fungal culture. In the meantime, the child was managed with ventricular tap. Later on, the shunt was placed on the opposite side, and the child was doing well.FIGURE 1: Whitish material in the shunt causing complete block.FIGURE 2: Photomicrograph showing fungal hyphae (left) that was characterized as A. fumigatus after culture (right).FIGURE 3: Photomicrograph showing fungal hyphaeDISCUSSION The central nervous system (CNS) involvement caused by Aspergillus species is very rare. This syndrome often manifests itself with fever and headache that may be present for several weeks before a diagnosis is established, and meningismus may be present but is nonspecific.2,5 Our child was not having any other complaints except a reincrease in the size of the head because the fungus was confined to the shunt system, and there was no systemic involvement. The CSF findings are inconclusive because, typically, only a small number of fungal cells are present in the CSF.3,6 Culture is the key to make the diagnosis, and it showed growth only in the shunt system, and there was no growth in the ventricular CSF in the present. This explains that, in the present case, the patient was not the source of infection as described in the literature;4 however, the shunt system got contaminated during the surgical procedure. The fact that establishing a diagnosis of CNS involvement due to Aspergillus is difficult and that many cases have been diagnosed only at autopsy indicates the gravity of the condition.7-9 Neutrophils (polymorphonuclear neutrophils) are the most important line of defense against Aspergillus hyphae, and they need the integrity of the immune system.1 The management of CNS aspergillosis is problematic because diagnosing the infection is difficult, and treatment should include a drug with activity against Aspergillus species that also penetrates into the CSF.5 Given the rarity of aspergillus meningitis, there is no standard therapy. Early antifungal treatment is the only chance of survival.3,5 Intravenous and intraventricular5,10 amphotericin B desoxycholate, itraconazole,11 and voriconazole2,5 have been tried in the management of cerebral aspergillosis with variable success. Despite increasing availability of antifungal drugs, the prognosis of cerebral aspergillosis is poor.2 These patients need a long-term treatment and follow-up.5 This case illustrates the importance of asepsis during surgery and careful handling of the shunt system during surgery.

Frontonasal malformation, first branchial arch anomalies, congenital heart defect, and severe central nervous system involvement: A possible “new” autosomal recessive syndrome?

Here we report on a girl presenting with midline cleft lip/palate, prominent forehead, macrocephaly, first branchial arch anomalies, and tetralogy of Fallot. Imaging studies showed polymicrogyria, enlarged ventricles with a large cystic lesion extending postero-superiorly over the cerebellum, abnormally modeled cerebellum, and congenital aqueductal stenosis. To our knowledge, this combination of clinical signs involving the frontonasal process, midline lip clefting, congenital heart malformation, and severe CNS developmental abnormalities has not previously been reported. Clinical, imaging data, as well as differential diagnosis are discussed.

Pathogenesis of Chiari II Malformation

Ependymal vimentin immunoreactivity was studied in necropsy specimens of brains and spinal cords of 14 patients with Chiari II malformations and 2 with congenital aqueductal stenosis without Chiari malformation at Cedars-Sinai Medical Center and UCLA School of Medicine, Los Angeles, CA.

Regional ependymal upregulation of vimentin in Chiari II malformation, aqueductal stenosis, and hydromyelia.

Vimentin, glial fibrillary acidic protein (GFAP) and S-100beta protein were studied by immunocytochemistry in the ependyma of patients with Chiari II malformations, congenital aqueductal stenosis, and hydromyelia. Paraffin sections of brains and spinal cords of 16 patients were examined, 14 with Chiari II malformations, most with aqueductal stenosis and/or hydromyelia as associated features, and 2 patients with congenital aqueductal stenosis without Chiari malformation. Patients ranged in age from 20-wk gestation to 48 years. The results demonstrated: 1) in the fetus and young infant with Chiari II malformations, congenital aqueductal stenosis, and hydromyelia, vimentin is focally upregulated in the ependyma only in areas of dysgenesis and not in the ependyma throughout the ventricular system; 2) GFAP and S-100beta protein are not coexpressed, indicating that the selective upregulation of vimentin is not simple maturational delay; 3) vimentin upregulation also is seen in the ependymal remnants of the congenital atretic cerebral aqueduct, not associated with Chiari malformation; 4) in the older child and adult with Chiari II malformation, vimentin overexpression in the ependyma becomes more generalized in the lateral ventricles as well, hence evolves into a nonspecific upregulation. The interpretation from these findings leads to speculation that it is unlikely that ependymal vimentin is directly involved in the pathogenesis of Chiari II malformation, but may reflect a secondary upregulation due to defective expression of another gene. This gene may be one of rhombomeric segmentation that also plays a role in defective programming of the paraxial mesoderm for the basioccipital and supraoccipital bones resulting in a small posterior fossa. This interpretation supports the hypothesis of a molecular genetic defect, rather than a mechanical cause, as the etiology of the Chiari II malformation.

The Impact of Endoscopic Third Ventriculostomy on the Management of Newly Diagnosed Hydrocephalus in Infants

Objectives: To evaluate the role of endoscopic third ventriculostomy (ETV) as a primary treatment for hydrocephalus in children less than 1 year old and to determine its impact as a whole on the reduction of shunts necessary in a new population of hydrocephalic infants. Methods: Data were collected prospectively on 47 infants with newly diagnosed hydrocephalus of all aetiologies who were referred between 1st April 1998 and 30th September 2000. Twenty-one patients (median age 6 weeks, range 34 weeks of gestation to 10 months) underwent ETV, while the remaining 26 patients had insertion of a ventriculoperitoneal shunt. Anatomical criteria and demonstration of third ventricle outflow obstruction on preoperative magnetic resonance imaging were used to select patients for ETV. Results: There was no mortality or major morbidity following ETV. The median follow-up period was 18 (range 8–36) months. During the follow-up period, the ETV remained patent in 7 (33%) of the 21 patients. Of the 14 patients with failed ETV, 11 had insertion of a ventriculoperitoneal shunt, while 3 have undergone successful redo ETV. Therefore, in total 10 patients (48%) of the ETV group remain shunt independent. The best results were obtained in patients with congenital aqueduct stenosis with 71% (5 of 7 patients) success rate, while patients with posthaemorrhagic hydrocephalus did particularly badly with only 1 of 10 patients having a successful ETV. Overall, 10 of 47 (21%) infants with newly diagnosed hydrocephalus have avoided a shunt. Conclusions: Our results suggest that the selective use of ETV as the primary treatment in infants with hydrocephalus is safe and can lead to a reduction in the shunted population of all newly diagnosed hydrocephalic infants by up to 21%. Success of ETV is aetiology, not age dependent.

Autosomal recessive hydrocephalus due to congenital stenosis of the aqueduct of Sylvius

Isolated hydrocephalus due to congenital stenosis of the aqueduct of Sylvius is almost always an X-linked recessive inherited condition. We describe a brother and sister with isolated hydrocephalus from congenital aqueductal stenosis. We believe that these two occurrences represent a rare autosomal recessive form of this abnormality. In assessing a first known occurrence of hydrocephalus with stenosis of the aqueduct of Sylvius in a family, the rare possibility of autosomal inheritance must be considered in genetic counselling.

Autosomal recessive hydrocephalus due to congenital stenosis of the aqueduct of Sylvius

Autosomal recessive hydrocephalus due to congenital stenosis of the aqueduct of Sylvius

Histochemistry and immunocytochemistry of the developing ependyma and choroid plexus.

The adult human ependyma expresses no intermediate filament proteins or secretory proteins; the fetal ependyma shows strong immunocytochemical (ICC) expression of vimentin, glial fibrillary acidic protein (GFAP), cytokeratins (CKs) of high molecular weight, glycoproteins, and S-100beta protein. Each has a precise and specific spatial distribution within the developing ependyma and a predictable time of appearance and regression in each region of the ventricular system. Several are coexpressed, but some appear earlier or persist longer than others. Secretory proteins of ependymal cells are important in several developmental processes such as the guidance of axonal growth cones. GFAP is not expressed in the floor plate ependyma at any stage of development, unlike vimentin and CK. The choroid plexus epithelium is a specialized ependyma, with an ICC profile that differs from the surface ependyma: vimentin, CK, and S-100beta protein continue to be expressed throughout fetal and adult life, but GFAP is not expressed. Certain cerebral malformations are associated with specific ICC abnormalities: ependymal S-100beta protein continues to be immunoreactive in disorders of neuroblast migration; ependymal vimentin is focally upregulated in Chiari malformations and congenital aqueductal stenosis. Other mammalian and nonmammalian species have characteristic profiles of ependymal immunoreactivity to the same proteins expressed in humans but exhibit interspecific differences.

Overexpression of nestin and vimentin in the ependyma of spinal cords from hydrocephalic infants

The ependyma of the spinal central canal in cases of hydrocephalus shows abnormalities which vary with the aetiology of ventricular dilatation. To determine whether these ependymal changes are developmental or reactive in nature, immunohistochemical findings were compared between nine normal controls and 12 cases of hydrocephalus (three each of congenital aqueductal stenosis. Dandy-Walker malformation, Chiari type II malformation, and post-haemorrhagic hydrocephalus) using antisera to nestin, vimentin and glial fibrillary acidic protein. The main pathological findings were disruption of ependymal layer, apparent pseudostratification of ependyma, expansion, cleft or syrinx formation in relation to the central canal, and ependymal rosette formation. In normal developing fetal spinal cord, nestin and vimentin were expressed mainly in pseudostratified ependymal cells and radial fibres in the median septum. In cases with congenital hydrocephalus (congenital aqueductal stenosis. Dandy-Walker malformation, and Chiari type II malformation), nestin was overexpressed in immature ependymal cells, and strong vimentin immunoreactivity was detected in the long tract of radial fibres in the median septum. Nestin and vimentin were also expressed in small cells and their fibres which covered areas denuded of ependymal cells in cases of Chiari type II malformation and post-haemorrhagic hydrocephalus. Two conclusions are suggested by this report. First, the ependyma of the spinal central canal in congenital hydrocephalus shows a delay in maturation of radial glial cells into mature astrocytes and ependymal cells. Second, areas of ependymal denudation may be repaired by the immature glial cells derived from subependymal cells.

Overexpression of nestin and vimentin in ependymal cells in hydrocephalus.

In order to elucidate the immunohistochemical features of hydrocephalic ependyma, immunohistochemical examination was undertaken in 11 normal, postmortem brains (age range, 11 weeks' postconception to 6 months after birth) and 12 hydrocephalic brains (three cases each of congenital aqueductal stenosis, Dandy-Walker malformation, Arnold-Chiari type II malformation and posthemorrhagic hydrocephalus) by using antisera to nestin, vimentin and glial fibrillary acidic protein (GFAP). In normal brains, nestin was predominantly expressed in neuroepithelial cells and radial glial fibers during the period of neuronal migration. Vimentin immunoreactivity was principally detected in immature ependymal cells and their basal fibers after the period of neuronal migration, then partly replaced by GFAP reactivity during late gestation. In hydrocephalus, the areas of ependymal disruption were covered with nestin- or vimentin-positive cells. Nestin and vimentin were also expressed in immature ependymal cells or their basal processes in anatomical regions such as the roof or floor plate of the fourth ventricle or the cerebral aqueduct, and the ventral part of the third ventricle. These results suggest that the overexpression of nestin and vimentin in hydrocephalus follows two patterns: a reactive pattern of proliferating immature glial cells associated with ependymal cell loss and an abnormal developmental pattern of immunopositivity associated with anatomical regions in the midline mesencephalon.

Experimental models of congenital hydrocephalus and comparable clinical problems in the fetal and neonatal periods.

Morphological and developmental changes of the ventricular system are analyzed in three major experimental models of congenital hydrocephalus in the rat: 6-aminonicotinamide (6-AN)-induced and LEW/Jms and HTX mutant hydrocephalus. The clinically comparable forms of hydrocephalus and problems occurring during each period of intrauterine hydrocephalus are then discussed. Comparative morphological study revealed that 6-AN-induced hydrocephalus was comparable to the Dandy-Walker syndrome and that the critical period regarding this syndrome in fetal life was at the time of "legal termination". The LEW/Jms and HTX mutant models were identical with regard to the form of progressive hydrocephalus in the postnatal period, but the condition underlying the hydrocephalus during the fetal period differed. The LEW/Jms model was comparable to primary congenital aqueductal stenosis (aqueductal agenesis), and the hydrocephalic state appeared in the period of "intrauterine preservation" before pulmonary maturation was completed. On the other hand, the HTX fetuses demonstrated secondary change of the aqueduct in the perinatal period, although the model was considered to be of congenital communicating hydrocephalus. Cerebrospinal fluid (CSF) dynamics studied in the fetuses with 6-AN-induced hydrocephalus disclosed considerable pathophysiology comparable to "hydromyelic hydrocephalus." The historical trends of animal experimental models of congenital hydrocephalus are reviewed and comparable clinical problems suggested by those models discussed further.

Mesencephalic and third ventricle cysts: diagnosis and management in four cases.

Four infants with obstructive hydrocephalus caused by space occupying third ventricle and mesencephalic cysts are reported. Despite immediate shunt insertion in all patients, there was either lack of clinical improvement or late onset of clinical deterioration. Neuroimaging (CT, MRI, and ventriculography) diagnosed the presence of non-communicating midline outpouchings of the CSF pathways causing obstruction of aqueductal CSF flow and brainstem signs. The cysts were of different origin. In one patient it was caused by a previous thalamic haemorrhage, in another patient by neonatal Escherichia coli meningoventriculitis. In two cases with obstructive hydrocephalus at birth, the aetiology is unclear. Direct puncture and drainage of the cysts led to clinical improvement. The cysts were poorly visualised on CT and could be misinterpreted as an enlarged third ventricle, simulating congenital aqueduct stenosis. Careful neuroradiological investigation is necessary to establish an accurate diagnosis and neurosurgical management. In such cases with hydrocephalus and persisting ventricular enlargement despite shunting, CT ventriculography is a useful tool.

Ventriculostomy for Treatment of Hydrocephalus

Ventriculostomy for hydrocephalus can either obviate completely or reduce considerably the complications of cerebrospinal fluid (CSF) shunts. Renewed interest in this procedure has followed the development of flexible and steerable neuroendoscopes, high-quality video cameras, endoscopic surgical instruments, including lasers, and methods of providing computer-guided stereotactic assistance. Ventriculostomy is the preferred treatment for patients with congenital aqueduct stenosis that requires CSF diversion. It is less successful in patients with acquired aqueduct stenosis but is still a treatment option. Interventriculostomy for treatment of intracranial cysts or loculated regions of the ventricles also can obviate or reduce the need for CSF shunts.

<I>A New Neurosurgical Ventriculoscope</I>

A new, flexible fiberoptic ventriculoscope for observation of the ventricles and major cisterns is reported. This device has been safely used to examine patients with obstructive hydrocephalus due to lesions within the lateral and third ventricles or to congenital aqueductal stenosis. With this instrument, a pineal tumor protruding into the third ventricle was successfully observed and photographed in situ.

Sensory and cognitive evoked potentials in a case of congenital hydrocephalus

We studied auditory and visual evoked potentials in D.W., a patient with congenital stenosis of the cerebral aqueduct. Head CT scans revealed marked hydrocephalus with expanded ventricles filling more than 80% of the cranium and compressing brain tissue to less than 1 cm in thickness. Despite the striking neuroanatomical abnormalities, however, the patient functioned well in daily life and was attending a local community college at the time of testing. Evoked potentials provided evidence of preserved sensory processing at cortical levels. Pattern reversal visual evoked potentials had normal latencies and amplitudes. Brain-stem auditory evoked potentials (BAEPs) showed normal wave V latencies. Na and Pa components of middle-latency AEP had normal amplitudes and latencies at the vertex, although amplitudes at lateral electrodes were larger than at the midline. In contrast to the normal sensory responses, long-latency auditory evoked potentials to standard and target tones showed abnormal P3 components. Standard tones (probability 85%), evoked NN1 components with normal amplitudes (−3.7 μV) and latencies (103 msec), but also elicited large P3 components (17 μV, latency 305 msec) that were never observed following frequent stimuli in control subjects. Target stimuli (probability 15%) elicited P3s in D.W. and controls, but P3 amplitudes were enhanced in D.W. (to more than 40 μV) and the P3 showed an unusual, frontal distribution. The results are consistent with a subcortical sources of the P300. Moreover, they suggest that the substitution of controlled for automatic processes may help high-functioning hydrocephalics compensate for abnormalities in cerebral structure.

Congenital absence of pyramids and its significance in genetic diseases.

Bilateral absence of the pyramids, best assessed in transverse sections of the medulla oblongata, was found in 0.7% of 2,850 autopsies performed at the Royal Children's Hospital, Melbourne (Australia). A strong association with some forms of congenital aqueductal stenosis was observed and evaluated in further cases ascertained through other hospitals. The very strong association observed with X-linked congenital aqueduct stenosis may be useful diagnostically but must be evaluated in other centres. At least, the presence of pyramids seems strong evidence against this diagnosis. Absence of the pyramids was also observed in several known or new genetic syndromes - Meckel's syndrome, the HARD syndrome, two sisters with congenital aqueductal stenosis and polydactyly and two families with microcephaly and arthrogryposis.

Posthemorrhagic hydrocephalus. Low incidence in very low birth weight neonates with intraventricular hemorrhage.

In addition to seizures and long-term neurodevelopmental handicaps, infants with intraventricular hemorrhage (IVH) are at risk for posthemorrhagic hydrocephalus (PHH), and the incidence of this problem in preterm infants with known IVH has been reported to vary from 25% to 74%. Over a 46-month period, 438 neonates of 1250-gm birth weight or less were admitted to this Newborn Special Care Unit, and 269 survived the first 36 postnatal hours. Of these, 265 patients underwent computerized tomography and/or cranial ultrasound scanning for evaluation of germinal matrix and/or intraventricular hemorrhage (GMH/IVH): 133 infants were found to have experienced GMH/IVH, and 27 of these died within the 1st postnatal week. Of the 95 survivors with GMH/IVH, 43 were known to have GMH only; the other 52 experienced IVH and were therefore at risk for PHH. Patients with GMH/IVH underwent repeat investigations for the development of ventriculomegaly and possible PHH. Only five patients with IVH developed PHH, defined as ventriculomegaly, elevated intracranial pressure, and increasing occipitofrontal head circumference. Serial cranial ultrasound studies of 95 other consecutively admitted patients in this birth-weight range revealed an equal incidence (45%) of low intracranial pressure ventriculomegaly in both the hemorrhage and non-hemorrhage groups, but none of them required shunting for hydrocephalus. One infant with congenital aqueductal stenosis was also identified.