Hydrocephalus In Infants Research Articles

Why a Focus Session on endoscopic third ventriculostomy in infants?

Since its “renaissance” in the late 1980s, endoscopic third ventriculostomy (ETV) gained a growing acceptance and, eventually, an established place in the surgical treatment of obstructive hydrocephalus. It soon became clear, however, that a part of the patients undergoing that endoscopic procedure eventually failed and that the chance of curing the hydrocephalus by endoscopy alone (without a shunt) depended on several factors, from which patient’s age and etiology of hydrocephalus are the most important. Most pediatric neurosurgeons agree that ETV has a higher failure rate in infants as opposed to children, adolescents, or adults. As some of us (not all) have found very low success rates in the first months of life, the question of whether this procedure should be offered at all to our youngest patients or whether it should be reserved to infants beyond the first or second year of life was raised. Similar considerations concern the role of etiology: there is general consensus that patients with isolated aqueductal stenosis are “good candidates” for ETV, whereas newborns with hydrocephalus in the context of myelomeningocele should be treated with shunts. But what kind of treatment should be chosen in other etiologies? How should mixed forms of obstructive/absorptive hydrocephalus be dealt with? Which kind of preoperative imaging is indispensable? Are there differences between ETV and shunts in the first year of life, with respect to complications or neurologic long-term outcome? This series of articles is intended to give an actual overview over the different important aspects of ETV in infants, particularly in the first year of life. The role of preoperative imaging, frequency and type of complications, and neurologic development after ETV vs shunt are dealt with, as well as the impact of age on success rate, indications for ETV in pathologies different from isolated aqueductal stenosis, or the relevance of a “spectrum classification” of absorptive vs obstructive hydrocephalus for the choice of the appropriate treatment procedures. Of course, this Focus Session not only gives more or less established answers, but also addresses questions that still remain open. In particular, the important issue of final neurodevelopmental outcome of children treated by ETVor shunt can be dealt with only by a prospective and randomized study, following the patients over years, as is intended to be realized by the ongoing International Infant Hydrocephalus Study (IIHS). While this Focus Session reflects our present knowledge, we are optimistic that the future will clarify questions that at the moment must be left unanswered. Childs Nerv Syst (2006) 22:1527 DOI 10.1007/s00381-006-0188-2

MR imaging study on external hydrocephalus in infants: extracerebral space developmental and pathological enlargement

目的 分析婴幼儿脑外积液的MRI特征,明确脑外积液的病因及与脑发育的关系.方法选择经MRI确诊的46例年龄＜2岁的脑外积液患儿,分析其MRI特征.并按月龄分7组,在T2WI上测量脑外间隙宽度并与正常值对照.结果引起婴幼儿脑外积液的主要原发病有感染性疾病、硬膜下或蛛网膜下出血、缺氧缺血性脑病(HIE)占67.4%(31/46例),原因不明占26.1%(12/46例).脑外积液主要发生在大脑凸面的前部,以蛛网膜下腔积液多见,占80.4%(37/46例),硬膜下积液8.7%(4/46例),硬膜下和蛛网膜下积液并存10.9%(5/46例).其中,化脓性脑膜炎可致硬脑膜或软脑膜的信号在T1WI或T2WI上增高,常引起硬膜下积液或与蛛网膜下腔积液并存.硬膜下和(或)蛛网膜下腔出血常为硬膜下和蛛网膜下腔积液并存,并常见大脑表面静脉(皮质静脉)增粗、淤滞和出血,在T1WI上信号增高.HIE所致脑外积液为蛛网膜下腔积液,可见HIE所致的特征性改变,常有髓鞘化落后占63.6%(7/11例).原因不明者多为双侧对称性的蛛网膜下腔积液.脑室扩大主要见于HIE和硬膜下或蛛网膜下出血.结论婴幼儿脑外积液多有明确病因,以出血、感染和HIE为多见,积液的部位与脑发育的特性有关,MRI对明确脑外积液的性质,判断病因有帮助。

Proposal of “evolution theory in cerebrospinal fluid dynamics” and minor pathway hydrocephalus in developing immature brain

The specificity of cerebrospinal fluid (CSF) dynamics in the immature brain still remains unknown. In our data previously published, the transependymal intraparenchymal CSF pathway (the minor pathway) plays a significant role in various degrees in the alternative CSF passage. Now, there is a growing consensus in the age differences in the outcome of neuroendoscopic ventriculostomy in treatment of non-communicating types of hydrocephalus. The authors discuss the clinical significance of the specific CSF dynamics and propose the new aspect of classification of hydrocephalus with a theory in the development of CSF from the pathophysiological point of view. Between January 2001 and March 2004, 122 hydrocephalic children were registered at the Jikei University Hospital Women's & Children's Medical Center (JWCMC), Tokyo. Our retrospective study for the efficacy of neuroendoscopic ventriculostomy confirmed the significantly high failure rate of neuroendoscopic ventriculostomy in treating hydrocephalus in neonates and infants with non-communicating hydrocephalus as the initial impression. The prospective CSF dynamic studies using cine-mode MRI and CT ventriculo-cisternography were then routinely started. Altogether, 9 out of 29 (31%) endoscopically treated cases needed shunt placement 3-30 weeks (mean 7.9 weeks) after the endoscopic procedure(s) (publication in preparation). Five out of 11 (45%) neonates/infants under 3 months, 3/5 (60%) infants at 7-12 months, 10/10 (100%) toddlers at 1-4 years and 3/3 (100%) schoolchildren at 5-17 years were cured, as in the condition of "post-endoscopic ventriculostomy arrested hydrocephalus". The pattern of ventriculo-cisternography in neonatal/infantile cases revealed intraparenchymal predominant pattern (minor pathway) of the CSF dynamics rather than passage in the major pathway. The various basic investigations in rodents, cats and monkeys have suggested that CSF is absorbed not via Pacchionian bodies as the last end of the major pathway, which do not exist in these animals and are recognized after infantile period in human, but through the choroids plexus and the periventricular fenestrated venous capillaries into the deep venous channel. The high incidence of "failure to arrest hydrocephalus" by neuroendoscopic ventriculostomy in fetal, neonatal and infantile periods was considered to depend on the specific CSF dynamics, in which the major CSF pathway has not developed and the minor pathway has a significant role. PROPOSAL OF THEORY: We herein propose a new aspect of classification for hydrocephalus with special reference to the CSF circulation in the minor CSF pathway, i.e. "minor pathway hydrocephalus", differentiating the conventional classification by Dandy (communicating and non-communicating) or Russell (non-obstructive and obstructive) as "major pathway hydrocephalus". We also herein propose a hypothesis that the CSF dynamics develop in the theory of evolution from the immature brain, as in the animals with the minor CSF pathway predominance, towards matured adult human brain together with completion of the major CSF pathway: the "evolution theory in CSF dynamics".

Comparison of endoscopic third ventriculostomy alone and combined with choroid plexus cauterization in infants younger than 1 year of age: a prospective study in 550 African children

The aim of this prospective study was to determine whether, and in which patients, the outcome for bilateral choroid plexus cauterization (CPC) in combination with endoscopic third ventriculostomy (ETV) was superior to ETV alone. A total of 710 children underwent ventriculoscopy as candidates for ETV as the primary treatment for hydrocephalus. The ETV was accomplished in 550 children: 266 underwent a combined ETV-CPC procedure and 284 underwent ETV alone. The mean and median ages were 14 and 5 months, respectively, and 443 patients (81%) were younger than 1 year of age. The hydrocephalus was postinfectious (PIH) in 320 patients (58%), nonpostinfectious (NPIH) in 152 (28%), posthemorrhagic in five (1%), and associated with myelomeningocele in 73 (13%). The mean follow up was 19 months for ETV and 9.2 months for ETV-CPC. Overall, the success rate of ETV-CPC (66%) was superior to that of ETV alone (47%) among infants younger than 1 year of age (p < 0.0001). The ETV-CPC combined procedure was superior in patients with a myelomeningocele (76% compared with 35% success, p = 0.0045) and those with NPIH (70% compared with 38% success, p = 0.0025). Although the difference was not significant for PIH (62% compared with 52% success, p = 0.1607), a benefit was not ruled out (power = 0.3). For patients at least 1 year of age, there was no difference between the two procedures (80% success for each, p = 1.0000). The overall surgical mortality rate was 1.3%, and the infection rate was less than 1%. The ETV-CPC was more successful than ETV alone in infants younger than 1 year of age. In developing countries in which a dependence on shunts is dangerous, ETV-CPC may be the best option for treating hydrocephalus in infants, particularly for those with NPIH and myelomeningocele.

The international infant hydrocephalus study: concept and rational

During the recent meetings of the International Study Group on Neuroendoscopy and the International Society for Pediatric Neurosurgery, the consensus view emerged that there is a need to assess the value and efficacy of neuroendoscopic procedures against shunting in a scientific manner, to resolve long-lasting debates on the subject. A prospective randomized, controlled trial of endoscopic third ventriculostomy vs shunting in children presenting under the age of 2 years with pure aqueduct stenosis is been proposed and organized (the International Infant Hydrocephalus Study, IIHS). The participating surgeons must adhere to the philosophy of randomization and be suitably experienced in endoscopic techniques in infants. The primary outcome of the trial will be the overall health-related quality of life of these children at 5 years of age. Hence, the study is focusing on the effect of surgery on neurodevelopment, rather than the less important issue of shunt or stoma survival, that has been debated extensively with no conclusion so far. Intention-to-treat analysis will be performed according to the first surgery. Secondary outcomes such as complication and reoperation rate, total hospitalization time and cost, need for repeat imaging, and others will be analyzed as well. Pure aqueduct stenosis is relatively rare, making recruitment problematic, but has been chosen to avoid other confounding factors that could influence outcome. More than 25 centers worldwide have committed already to patient recruitment to the study. It is anticipated that recruitment will last for 2 years, aiming for 91 patients per arm. The study has started recruiting patients already in some countries. It is hoped that the trial will not only provide answers to unsettled debates on the value of neuroendoscopy but also create a network of collaborating pediatric neurosurgeons for future initiatives.

Intramedullary capillary hemangioma associated with hydrocephalus in an infant

This 3-month-old child presented with an enlarging head circumference arising from communicating hydrocephalus with large subarachnoid spaces in the posterior fossa. Neuroimaging performed to clarify the origin and pathogenesis of the hydrocephalus revealed a vascular lesion within the dorsal spinal cord. Insertion of a cerebrospinal fluid shunt and total removal of the spinal tumor were performed successfully. Histological examination of the medullar lesion demonstrated a capillary hemangioma. Proposed mechanisms for increased intracranial pressure and spinal cord lesions are presented. A spinal hemangioma in this age range associated with hydrocephalus has not been reported previously, but spinal lesions must be considered in the presence of hydrocephalus with no clear origin.

Ventriculosubgaleal Shunts for Posthemorrhagic Hydrocephalus in Premature Infants

Objective: The early management of posthemorrhagic hydrocephalus in premature infants is challenging and controversial. These infants need a temporary cerebrospinal fluid (CSF) diversion procedure until they gain adequate weight, and the blood and protein levels in CSF are reasonably low before permanent shunt can be placed. Various options are available with their associated advantages and disadvantages. Ventriculosubgaleal shunts have been recommended as a more physiologic and less invasive means of achieving this goal. We have performed this procedure in 6 premature infants to evaluate their effectiveness and complications. Methods: Six consecutive premature infants with posthemorrhagic hydrocephalus underwent placement of ventriculosubgaleal shunts over a 1-year period of time. We reviewed their clinical and imaging progress to assess the ability of the shunt to control hydrocephalus and the complication rates. Results: In all 6 patients, the ventriculosubgaleal shunt controlled the progression of hydrocephalus as assessed by clinical and imaging parameters. A permanent shunt was avoided in 1 patient (16.6%). However, 4 patients developed shunt infections, 1 involving the ventriculosubgaleal shunt itself, and 3 immediately after conversion to ventriculoperitoneal shunt. The total infection rate of the series was 66.6%. All infections were caused by staphylococcus species. There was only a 1% shunt infection rate in our institution for all nonventriculosubgaleal shunts during the same period of time. Conclusion: Placement of ventriculosubgaleal shunts for interim CSF diversion in neonates with posthemorrhagic hydrocephalus is effective as a temporary method of CSF diversion. However, our experience has shown that it is associated with a unacceptably high CSF infection rate. A potential cause for infection is CSF stasis just beneath the extremely thin skin of the premature infants, promoting colonization by skin flora. CSF sampling before conversion to a permanent shunt and replacement of the proximal hardware, which has been in situ for a prolonged period, may decrease the infection rates. At present, the procedure is no longer performed at our institution.

Accumulation of Transforming Growth Factor-β2 and Nitrated Chondroitin Sulfate Proteoglycans in Cerebrospinal Fluid Correlates with Poor Neurologic Outcome in Preterm Hydrocephalus

Background: Progressive post-hemorrhagic hydrocephalus in preterm infants strongly predicts abnormal neurologic development, and often accompanies cystic periventricular leukomalacia (cPVL). Transforming growth factor-β₁ (TGF-β₁), associated with hydrocephalus, can upregulate the chondroitin sulfate proteoglycan (CSPG) synthesis. To date, CSPG and their nitrated metabolites (NT-CSPG) have not been evaluated in hydrocephalus. Objectives: We hypothesized that TGF-β₁, TGF-β₂, CSPG, and NT-CSPG would accumulate in cerebrospinal fluid (CSF) in preterm hydrocephalus, and their concentrations would correlate with poor long-term outcomes. Methods: TGF-β₁, TGF-β₂, CSPG, and NT-CSPG concentrations in CSF were measured prospectively by ELISA in 29 preterm newborns with (n = 22) or without (n = 34) progressive post-hemorrhagic hydrocephalus, and correlated with progressive neonatal hydrocephalus and neurologic outcome. Only concentrations from each patient’s initial CSF sample were used for statistical analysis. Results: Compared to neonates without hydrocephalus, CSF [TGF-β₁], [TGF-β₂], [CSPG] and [NT-CSPG] were significantly greater by >3-, >35-, >8-, and >3-fold, respectively. Unlike CSF [TGF-β₂] and [CSPG], [TGF-β₁] correlated with CSF [total protein]. Only CSF [NT-CSPG] correlated with cPVL. Unlike [TGF-β₂] or [CSPG], [NT-CSPG] correlation with preterm progressive post-hemorrhagic hydrocephalus (PPHH) was explained entirely by the presence of cPVL among these patients. [TGF-β₂] was >20-fold greater in preterm survivors who required a ventriculoperitoneal shunt for PPHH (n = 9), as compared to survivors who did not require a shunt (n = 2), or those without hydrocephalus (n = 12). [TGF-β₂] and [NT-CSPG] correlated inversely with Bayley Index Scores (15.0 months median adjusted age). Conclusions: This is the first report that [TGF-β₂], [CSPG], and [NT-CSPG], measured well before term, accumulate abnormally in preterm progressive post-hemorrhagic hydrocephalus CSF, and correlate with adverse neurologic outcome.

Experiences with hydrostatic valves in the treatment of hydrocephalus in infancy and childhood

Introduction: The choice of the specific valve seems to be very important in the treatment of the childish hydrocephalus. In this study 53 children were treated with hydrostatic valves. The experiences with these valves over a period of 7 years are demonstrated here.

Questions and answers

Hydrocephalus is described as a multifactorial condition characterized by excessive accumulation of cerebrospinal fluid (CSF) within the ventricles, which causes dilatation of the ventricles. CSF is produced at a consistent rate of 0.3 milliliters per minute. If the amount produced is greater than the amount absorbed, the ventricles enlarge, eventually causing the lining of the ventricles and then the underlying white matter to be disrupted. This results in expansion of the skull and thinning and atrophy of the brain ( James, 1992 James H.E. Hydrocephalus in infancy and childhood. American Family Physician. 1992; 45: 733-742 PubMed Google Scholar ). Classification of hydrocephalus can be based on a variety of factors. For the purpose of this article, the classifications of “congenital” and “acquired” hydrocephalus will be used. Causes of congenital hydrocephalus include intrauterine infections and genetic abnormalities. Acquired hydrocephalus can be due to acquired infection, neoplasms, vascular damage, or malformations and trauma. The incidence of congenital hydrocephalus is approximately 4 of every 1,000 live births and may be diagnosed prenatally by ultrasound and/or is overt at birth. When diagnosed prenatally, a cesarean delivery is indicated due to the probability of cranio-pelvic disproportion.

Postmeningitic bacterial hydrocephalus in infancy: report of 23 cases and review of the literature

Despite hydrocephalus being a frequent bacterial meningitis complication , there are few reports pertaining to this subject in the literature. In fact, we found only 13 reports which included this etiological description […] Postmeningitic bacterial hydrocephalus in infancy: report of 23 cases and review of the literature

Adults with Hydrocephalus Treated in Infancy and Childhood

This review considers the unique pathophysiologies and problems confronting adults who have been treated for hydrocephalus since infancy. Most of these patients will have to change the setting in which they receive care. Therefore, general neurosurgeons who will become the new caretakers for these adult patients must understand the challenges involved. Hydrocephalus in adults has a limited number of origins, and a limited number of points of obstruction can cause the condition. In contrast, congenital conditions that cause hydrocephalus can lead to multiple points of obstruction, making management of these infants difficult. Infants also have distensible heads, which can lead to unique causes of hydrocephalus. Intracranial venous hypertension causes pseudotumor cerebri in adults but it is a rather common cause of hydrocephalus in infants with distensible heads. The most common cause of infantile hydrocephalus is spina bifida associated with a Chiari II malformation. There are four different points of obstruction in these patients, each manifesting with a unique syndrome at the time of shunt failure. The concept of shunt dependency is being redefined as the popularity of endoscopic third ventriculostomy increases. Although the use of the technique in the context of spina bifida remains controversial, the procedure may allow more than 70% of children shunted in infancy whose ventricles expand at the time of shunt failure to live without a shunt. Unlike adults, 20% of infants who are still shunt dependent as adults will have very high intracranial pressure at the time of shunt failure even though the ventricles do not expand. A significant percentage of these patients will benefit from a valve-regulated lumboperitoneal shunt. Any adult who experiences ventricular dilatation at the time of shunt failure should be considered a candidate for endoscopic third ventriculostomy.

Long-term functional evaluation of congenital hydrocephalus in infants and children.

In the past 20 years, 43 patients with congenital hydrocephalus underwent surgical treatment for hydrocephalus in our clinic (Myelomeningocele, Dandy-Walker syndrome, holoprosencephaly and hydranencephaly, which are frequently associated with dysgenesis of the corpus callosum, were excluded). The gestational stage at the onset of hydrocephalus was assessed on the basis of the morphology of the corpus callosum. The patients were then divided into four groups according to stage of onset. A relation between the stage of onset and the long-term functional scores was demonstrated. The earlier the gestational stage at which the hydrocephalus occurred, the lower was the long-term functional score.

Posthemorrhagic hydrocephalus in preterm infants: long-term follow-up and shunt-related complications.

A retrospective analysis of 42 preterm infants with intraventricular hemorrhage was performed in order to evaluate shunt-related problems in neonates with posthemorrhagic hydrocephalus. Within the last 15 years, 76 infants with intraventricular hemorrhage were treated primarily by external ventricular drainage, and 42 needed permanent shunting. Shunting was performed 28-101 days after the patients' birth, ventriculoatrial shunts being placed in 10 patients and ventriculoperitoneal shunts in 32. The mean number of shunt revisions per patient was 1.57. The main reasons for shunt revision were infection (7.1%) and blockage (45.2%). Primary ventriculoperitoneal and ventriculoatrial shunts differed only insignificantly in revision rate and length of shunt survival, whereas ventriculoperitoneal shunts used in shunt revisions required significantly fewer further revisions. The neurological outcome was not related to the necessity for or to complications of a shunt. Programmable valve systems and neuroendoscopy appear to be helpful in the overall management and in the treatment of complications.

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.

Fetal Surgery for Myelomeningocele and the Incidence of Shunt-Dependent Hydrocephalus

ContextIntrauterine closure of exposed spinal cord tissue prevents secondary neurologic injury in animals with a surgically created spinal defect; however, whether in utero repair of myelomeningocele improves neurologic outcome in infants with spina bifida is not known.ObjectiveTo determine whether intrauterine repair of myelomeningocele improves patient outcomes compared with standard care.DesignSingle-institution, nonrandomized observational study conducted between January 1990 and February 1999.SettingTertiary care medical center.ParticipantsA sample of 29 study patients with isolated fetal myelomeningocele referred for intrauterine repair that was performed between 24 and 30 gestational weeks and 23 controls matched to cases for diagnosis, level of lesion, practice parameters, and calendar time. All infants were followed up for a minimum of 6 months after delivery.Main Outcome MeasuresRequirement for ventriculoperitoneal shunt placement, obstetrical complications, gestational age at delivery, and birth weight for study vs control subjects.ResultsThe requirement for ventriculoperitoneal shunt placement for decompression of hydrocephalus was significantly decreased among study infants (59% vs 91%; P = .01). The median age at shunt placement was also older among study infants (50 vs 5 days; P = .006). This may be explained by the reduced incidence of hindbrain herniation among study infants (38% vs 95%; P<.001). Following hysterotomy, study patients had an increased risk of oligohydramnios (48% vs 4%; P = .001) and admission to the hospital for preterm uterine contractions (50% vs 9%; P = .002). The estimated gestational age at delivery was earlier for study patients (33.2 vs 37.0 weeks; P<.001), and the birth weight of study neonates was less (2171 vs 3075 g; P<.001).ConclusionsOur study suggests that intrauterine repair of myelomeningocele decreases the incidence of hindbrain herniation and shunt-dependent hydrocephalus in infants with spina bifida, but increases the incidence of premature delivery.

Fetal surgery for myelomeningocele and the incidence of shunt-dependent hydrocephalus.

Intrauterine closure of exposed spinal cord tissue prevents secondary neurologic injury in animals with a surgically created spinal defect; however, whether in utero repair of myelomeningocele improves neurologic outcome in infants with spina bifida is not known. To determine whether intrauterine repair of myelomeningocele improves patient outcomes compared with standard care. Single-institution, nonrandomized observational study conducted between January 1990 and February 1999. Tertiary care medical center. A sample of 29 study patients with isolated fetal myelomeningocele referred for intrauterine repair that was performed between 24 and 30 gestational weeks and 23 controls matched to cases for diagnosis, level of lesion, practice parameters, and calendar time. All infants were followed up for a minimum of 6 months after delivery. Requirement for ventriculoperitoneal shunt placement, obstetrical complications, gestational age at delivery, and birth weight for study vs control subjects. The requirement for ventriculoperitoneal shunt placement for decompression of hydrocephalus was significantly decreased among study infants (59% vs 91%; P = .01). The median age at shunt placement was also older among study infants (50 vs 5 days; P = .006). This may be explained by the reduced incidence of hindbrain herniation among study infants (38% vs 95%; P<.001). Following hysterotomy, study patients had an increased risk of oligohydramnios (48% vs 4%; P = .001) and admission to the hospital for preterm uterine contractions (50% vs 9%; P = .002). The estimated gestational age at delivery was earlier for study patients (33.2 vs 37.0 weeks; P<.001), and the birth weight of study neonates was less (2171 vs 3075 g; P<.001). Our study suggests that intrauterine repair of myelomeningocele decreases the incidence of hindbrain herniation and shunt-dependent hydrocephalus in infants with spina bifida, but increases the incidence of premature delivery.

HLA-class II genes modify outcome of Toxoplasma gondii infection

Associations between Human Leukocyte Antigen (HLA) (i.e. human major histocompatibility complex [MHC]) genes and susceptibility to infections and inflammatory processes have been described, but causal relationships have not been proven. We characterized effects of HLA-DQ alleles on outcome of congenital toxoplasma infection and found that among Caucasians, the DQ3 gene frequency was significantly higher in infected infants with hydrocephalus (0.783) than infected infants without hydrocephalus (0.444) or published normal controls (0.487). We then developed a novel animal model to definitively determine the effect of these HLA DQ molecules on the severity of toxoplasmosis. Human MHC-Class II transgenes reduced parasite burden and necrosis in brains of mice infected with Toxoplasma gondii. Consistent with the observed association between DQ3 and hydrocephalus in human infants, in the murine model the DQ3(DQ8; DQB1∗0302) gene protected less than DQ1 (DQ6; DQB1∗0601). Our findings definitively prove a cause and effect relationship between human MHC genes and resistance to infection, provide novel means to characterise human immune responses that are protective or pathogenic in infections, and are important for vaccine development.

Fibrinolytic agents in the management of posthemorrhagic hydrocephalus in preterm infants: the evidence.

The objective of this study was to review current literature on the management of posthemorrhagic hydrocephalus in preterm infants with intraventricular administration of fibrinolytic agents; to this end a literature search was carried out electronically. The keywords used were "intraventricular hemorrhage" or "posthemorrhagic hydrocephalus" in combination with "fibrinolytic agent," "urokinase," "streptokinase," or "recombinant tissue plasminogen activator" and "intraventricular administration"; the search covered the years 1966-1998 and was restricted to English language papers and human subjects. It was supplemented by a search through the reference lists of the articles identified. Articles dealing with intracerebral hemorrhage or hematoma, intraventricular hemorrhage in adults, nontherapeutic issues and laboratory research were excluded. The articles included are summarized in evidence and evaluation tables. Five scientific publications evaluating the use of a fibrinolytic agent to manage posthemorrhagic hydrocephalus were retrieved. In the studies described in these reports, a total of 62 neonates received streptokinase, urokinase or r-tPA intraventricularly. No two of the regimens were identical in the drug used, method of administration and duration of therapy. The time before therapy was started ranged from 2 to 35 days after the ictus. Among the case series reported, three were small series with a total of 38 neonates. One other case series of 18 neonates compared the treatment group with an historical control group. All case series showed that endoventricular fibrinolytic therapy was practical. The proportion of cases in which shunt placement was performed ranged from 11% to 100%. Only one small prospective, randomized, controlled study was identified. That study was too small to allow useful conclusions. Overall, 3 cases of secondary intraventricular hemorrhage were reported. However, it was not possible to determine with certainty whether these episodes were related to the drug therapy itself. The reports suffer from inadequate study design, lack of descriptive information and short follow-up period. There is insufficient evidence to justify the claim that fibrinolytic agents administered intraventricularly in posthemorrhagic hydrocephalus are safe and effective. More evidence is needed to prove or disprove the effectiveness and safety of this form of therapy.

Posthemorrhagic hydrocephalus and brain injury in the preterm infant: Dilemmas in diagnosis and management

Advances in neonatal critical care have reduced the incidence of intraventricular hemorrhage (IVH) in the newborn. Paradoxically, however, the prevalence of the complications of IVH including posthemorrhagic hydrocephalus (PHHC) has increased. By virtue of its association with long-term neurodevelopmental disability, posthemorrhagic hydrocephalus is an ominous diagnosis in the premature infant. Animal models have demonstrated that ventricular distention may cause direct cerebral parenchymal injury. Evidence for secondary parenchymal injury in the premature infant with PHHC is by necessity indirect. The precise impact of secondary parenchymal injury on the overall neurological outcome of premature infants with PHHC remains unclear in large part because of the vulnerability of the immature brain to other forms of injury (e.g., periventricular leukomalacia) that may be difficult to distinguish from injury due to distention. Furthermore, parenchymal injury due to PVL may cause ventricular enlargement that does not benefit from CSF diversion. Because these primary and secondary mechanisms of injury may operate concurrently, the precise or dominant cause of ventricular enlargement is often difficult to establish with certainty in the neonatal period. These diagnostic dilemmas have in turn impeded the development and evaluation of therapies specifically aimed at reversing ventricular distention and preventing secondary parenchymal injury. This article focuses on the current dilemmas in diagnosis and management of this potentially reversible form of injury as well as on potential future strategies for its prevention.