Prenatal presentation of a rare genetic disorder: a clinical, autopsy and molecular correlation

Walker Warburg syndrome (WWS) lies at the severe end of the spectrum of the congenital muscular dystrophies. WWS is a congenital disorder of the O-glycosylation that disrupts in the post-translation modification of dystroglycan proteins. WWS is characterized by the involvement of the central nervous system and rarely by multisystem involvement. Next-generation sequencing discovered that multiple genes are associated with this disorder. FKTN is the rarest cause of WWS. We describe a clinical-autopsy report of a molecularly- confirmed WWS case presenting with ventriculomegaly, agenesis of the corpus callosum with a novel phenotype of Dandy-Walker malformation and unilateral multi-cystic kidney. The whole-exome sequencing confirmed a homozygous variant (c.411C>A) in the FKTN gene with a premature termination codon. This case emphasizes the importance of detailed postnatal phenotyping through an autopsy in any pregnancy with antenatally identified malformations. Obstetricians, pediatricians as well as fetal medicine experts need to counsel the parents and focus on preserving the appropriate sample for genetic testing. WWS, though rare deserves testing especially in the presence of positive family history. Dandy-Walker malformation is a novel feature and expands the phenotypic spectrum.

Neurogenic pulmonary edema due to ventriculo-atrial shunt dysfunction: a case report / Edema pulmonar neurogênico devido à disfunção da derivação ventrículo-atrial: relato de caso

ABSTRACT BACKGROUND AND OBJECTIVES: Pulmonary edema is caused by the accumulation of fluid within the air spaces and the interstitium of the lung. Neurogenic pulmonary edema is a clinical syndrome characterized by the acute onset of pulmonary edema following a significant central nervous system insult. It may be a less-recognized consequence of raised intracranial pressure due to obstructive hydrocephalus by blocked ventricular shunts. It usually appears within minutes to hours after the injury and has a high mortality rate if not recognized and treated appropriately. CASE REPORT: We report a patient with acute obstructive hydrocephalus due to ventriculo-atrial shunt dysfunction, proposed to urgent surgery for placement of external ventricular drainage, who presented with neurogenic pulmonary edema preoperatively. She was anesthetized and supportive treatment was instituted. At the end of the procedure the patient showed no clinical signs of respiratory distress, as prompt reduction in intracranial pressure facilitated the regression of the pulmonary edema. CONCLUSIONS: This report addresses the importance of recognition of neurogenic pulmonary edema as a possible perioperative complication resulting from an increase in intracranial pressure. If not recognized and treated appropriately, neurogenic pulmonary edema can lead to acute cardiopulmonary failure with global hypoperfusion and hypoxia. Therefore, awareness of and knowledge about the occurrence, clinical presentation and treatment are essential.

RESUMO JUSTIFICATIVA E OBJETIVOS: o edema pulmonar é causado pelo acúmulo de líquido nos alvéolos e no interstício pulmonar. Edema pulmonar neurogênico é uma síndrome clínica caracterizada por edema pulmonar de início agudo após um acometimento súbito do sistema nervoso central. Pode ser uma consequência menos reconhecida de pressão intracraniana aumentada por causa da hidrocefalia obstrutiva por derivações ventriculares bloqueadas. Geralmente aparece em minutos ou horas após o insulto e tem uma alta taxa de mortalidade, caso não seja identificado e tratado adequadamente. RELATO DE CASO: relatamos o caso de paciente com hidrocefalia obstrutiva aguda por causa da disfunção da derivação ventrículo-atrial, programado para cirurgia em caráter de urgência para a colocação de derivação ventricular externa, que apresentou edema pulmonar neurogênico no pré-operatório. A paciente foi anestesiada e o tratamento de manutenção instituído. No fim do procedimento, a paciente não apresentou quaisquer sinais de distúrbio respiratório, pois a redução rápida da pressão intracraniana facilitou a regressão do edema pulmonar. CONCLUSÕES: este relato aborda a importância da identificação de um edema pulmonar neurogênico como uma possível complicação no período perioperatório resultante de um aumento da pressão intracraniana. Quando não identificado e tratado adequadamente, o edema pulmonar neurogênico pode levar à insuficiência cardiorrespiratória aguda, com hipoperfusão global e hipóxia. Portanto, a conscientização e o conhecimento de sua ocorrência, apresentação clínica e seu tratamento são essenciais.

Cráneo en trébol y fisura facial bilateral / Cloverleaf skull and bilateral facial clefts

Introducción: El síndrome del cráneo en trébol, o síndrome de Kleeblattschädel, es una malformación rara en la cual el cráneo presenta un aspecto de trébol. Es causado por el cierre prematuro de varias suturas, evidenciándose desde antes del nacimiento. Objetivo: presentar nuestra experiencia en un caso de síndrome del cráneo en trébol, y actualizar la información de la literatura. Caso clínico: lactante de sexo femenino, 5 meses de edad, diagnósticos al nacimiento de Fisura labio-Palatina e Hidrocefalia. A los 30 días de vida se instaló válvula ventrículo peritoneal, y se procedió a enucleación ocular bilateral por proceso infeccioso. Se controla en Genética donde se confirma macrocefalia y craneosinostosis tipo cráneo en trébol. El estudio citogenético 46XX, Ecocardiografía normal, TAC de cerebro mostró anomalias múltiples asociadas a hidrocefalia y malformaciones inespecíficas. Conclusión: El cráneo en trébol puede presentarse aisladamente o asociado a otras anomalías congénitas, conformando varios síndromes de craneosinostosis, como Crouzon, Pfeiffer o Carpenter. También puede ser componente de la secuencia de rotura amniótica o de diversas displasias, como la campomélica, tanatofórica tipo ii, o la distrofia torácica asfixiante de Jeune. El caso descrito no cumple con todas las características necesarias para incluirlo dentro de un síndrome específico, y no habiendo antecedentes familiares que sugieran patrón de herencia ni anomalías cromosómicas se concluye que se trata de un caso de anomalías congénitas de presentación esporádica.

Introduction: Cloverleaf skull syndrome, or Kleeblattschädel syndrome, is a rare malformation in which the skull has a cloverleaf appearance. It is caused by the premature closure of several sutures, being evident before birth. Objective: To present our experience in a case of cloverleaf skull syndrome, and update the information from the literature. Clinical case: A female infant of 5 months of age, diagnosed at birth with cleft lip and palate and hydrocephaly. A peritoneal ventricle valve was implanted at 30 days of life, and an ocular enucleation was performed due to an infectious process. The patient was followed-up in Genetics, where it confirmed a macrocephaly and craniosynostosis type cloverleaf skull. The 46XX cytogenetic study and echocardiography were normal. The brain CT scan showed multiple anomalies associated with hydrocephaly and non-specific malformations. Conclusion: Cloverleaf skull may be present in isolated form or associated with other congenital abnormalities, leading to various craniosynostosis syndromes, such as Crouzon, Pfeiffer or Carpenter. It may also be a component of the amniotic rupture sequence or to different dysplasias, such as campomelic dysplasia, thanatophoric dysplasia type 2, or the asphyxiating thoracic dystrophy of Jeune. The case presented does not fulfil all the characteristics needed to be included within a specific syndrome, and on not having a family history that suggests a hereditary pattern or chromosome abnormalities, it is concluded that it is a case of a congenital anomaly of sporadic presentation.

0.1T magnetic resonance image in the study of experimental hydrocephalus in rats. Accuracy of the method in the measurements of the ventricular size / Imagem de ressonância magnética de 1,0T no estudo da hidrocefalia experimental em ratos. Avaliação do método de medição do tamanho ventricular

PURPOSE: To investigate the accuracy of 1.0T Magnetic Resonance Imaging (MRI) to measure the ventricular size in experimental hydrocephalus in pup rats. METHODS: Wistar rats were subjected to hydrocephalus by intracisternal injection of 20% kaolin (n=13). Ten rats remained uninjected to be used as controls. At the endpoint of experiment animals were submitted to MRI of brain and killed. The ventricular size was assessed using three measures: ventricular ratio (VR), the cortical thickness (Cx) and the ventricles area (VA), performed on photographs of anatomical sections and MRI. RESULTS: The images obtained through MR present enough quality to show the lateral ventricular cavities but not to demonstrate the difference between the cortex and the white matter, as well as the details of the deep structures of the brain. There were no statistically differences between the measures on anatomical sections and MRI of VR and Cx (p=0.9946 and p=0.5992, respectively). There was difference between VA measured on anatomical sections and MRI (p<0.0001). CONCLUSION: The parameters obtained through 1.0T MRI were sufficient in quality to individualize the ventricular cavities and the cerebral cortex, and to calculate the ventricular ratio in hydrocephalus rats when compared to their respective anatomic slice.

OBJETIVO: Investigar a fidelidade das Imagens de Ressonância Magnética de 1,0T no estudo do tamanho ventricular na hidrocefalia experimental em ratos jovens. MÉTODOS: Ratos Wistar foram submetidos à hidrocefalia através da injeção intracisternal de caulim 20%. Dez animais permaneceram sem injeção para uso como controles. Ao final do experimento, os animais foram submetidos à Ressonância magnética de encéfalo e sacrificados. O tamanho ventricular foi avaliado por três medidas: razão ventricular (VR), espessura cortical (Cx) e área ventricular (VA), tomadas em fotografias das secções anatômicas e nas imagens de ressonância magnética (RM). RESULTADOS: As imagens por RM apresentaram qualidade suficiente para individualizar os ventriculos laterais, mas a distinção entre córtex e substância branca, bem como detalhamento das estruturas profundas do encéfalo não foram possíveis. Quando comparadas as medidas em seções anatômicas e RM, não houve diferença estatística entre as médias de razão ventricular e espessura cortical (p=0,9946 e p=0,5992, respectivamente). Houve diferença da área ventricular comparando-se as secções anatômicas e ressonância magnética (p<0,0001). CONCLUSÃO: Os parâmetros obtidos através de imagens da ressonância magnética de 1,0T foram suficientes para individualizar as cavidades ventriculares e o córtex cerebral, e para calcular o tamanho ventricular em ratos hidrocefálicos quando comparados aos seus respectivos cortes anatômicos.

Fenômeno ocular do sol poente em hidrocefalia. Apresentação de casos e revisão da literatura / Setting-sun ocular phenomenon in hydrocephalus. Case reporter of the literature

Introdução: O fenômeno do olho do "sol poente" é um sinal oftalmológico em que os olhos se apresentam dirigidos para baixo, deixando a esclera bem visível, entre a pálpebra superior e a íris, geralmente está associado com hipertensão intracraniana e hidrocefalia na infância. Entretanto, pode ser decorrente de patologias benignas, representadas pela imaturidade dos sistemas de controle reflexo dos movimentos oculares. Pacientes e métodos: Trabalho retrospectivo e descritivo. Foram estudadas 25 crianças de ambos os gêneros, portadoras de hidrocefalia, que foram diagnosticadas através de exames de neuroimagem e tratamento cirúrgico. Resultados: O gênero masculino esteve presente em 16 casos e o feminino em 9 casos. As causas de hidrocefalia foram: estenose do aqueduto de Silvius 14 casos, pós-mielomeningocele lombossacra 8 casos e toxoplasmose congênita 3 casos. Todos foram submetidos a exame de tomografia computadorizada e seis a ressonância magnética. Dos pacientes, 12 apresentavam o fenômeno do ?sol poente?. Todos foram submetidos à derivação ventriculoperitoneal. Houve reintervenção cirúrgica em sete casos; dois pacientes foram a óbito. Conclusão: O fenômeno do ?sol poente? é um sinal de alerta que indica lesão cerebral grave subjacente. A patogênese deste sinal não está bem esclarecida; acredita-se estar relacionado à distensão do aqueduto cerebral, com compressão de estruturas periaquedutais, secundária ao aumento da pressão intracraniana. Pode estar associado com hidrocefalia e disfunção do sistema de derivação ventriculoperitoneal. O diagnóstico precoce, com a realização de exames de neuroimagem, proporciona uma intervenção cirúrgica imediata e evita complicações neurológicas graves.

Magnetic resonance imaging of central nervous system tuberculosis: an experience of 50 cases from central India

Central Nervous System Tuberculosis [CNSTB] continues to be a common problem world-wide and particularly in India. With the widespread availability of Magnetic Resonance Imaging [MRI], it is increasingly used for the diagnosis and follow up of CNSTB. This study presents a review of 50 cases of CNSTB seen in central India. Between 2006 and 2009, 50 cases of CNSTB [28 Spinal, 22 Cerebral] were diagnosed and followed up. MRI was performed using either a0.2Tor 1.5T unit using a standard protocol. Contrast study was needed in 32 cases. The diagnosis was later confirmed either by histopathological or microbiological examination in most cases and by a positive treatment response in some cases. All patients underwent routine radiograph of the chest to look for associated pulmonary tuberculosis, haematological tests and in some cases CT scan guided aspiration / biopsy and CSF analysis. There were 20 male and 30 female patients with age range of 4 to 65 years. Most common spinal lesion noted was the typical paradiscal involvement followed by skip lesion and posterior element lesion. The lesion was extradural in 19 and intradural in 3 cases. The most common cerebral lesion was meningitis followed by tuberculomas, abscess and obstructive hydrocephalus. Response to treatment was assessed using MRI in 30 cases. MRI has revolutionized the imaging of CNSTB. The diagnosis can be made with reasonable certainty, obviating the need for an invasive procedure both for diagnosis and treatment. This was confirmed by the resolution of brain and spinal cord pathological changes after anti-tubercular chemotherapy. MRI also allows for monitoring the response to treatment of patients with CNSTB. However in some cases confirmation of diagnosis by needle aspiration and histopathological analysis may be indicated when the imaging findings are not conclusive

A cell junction pathology of neural stem cells leads to abnormal neurogenesis and hydrocephalus

Most cells of the developing mammalian brain derive from the ventricular (VZ) and the subventricular (SVZ) zones. The VZ is formed by the multipotent radial glia/neural stem cells (NSCs) while the SVZ harbors the rapidly proliferative neural precursor cells (NPCs). Evidence from human and animal models indicates that the common history of hydrocephalus and brain maldevelopment starts early in embryonic life with disruption of the VZ and SVZ. We propose that a "cell junction pathology" involving adherent and gap junctions is a final common outcome of a wide range of gene mutations resulting in proteins abnormally expressed by the VZ cells undergoing disruption. Disruption of the VZ during fetal development implies the loss of NSCs whereas VZ disruption during the perinatal period implies the loss of ependyma. The process of disruption occurs in specific regions of the ventricular system and at specific stages of brain development. This explains why only certain brain structures have an abnormal development, which in turn results in a specific neurological impairment of the newborn. Disruption of the VZ of the Sylvian aqueduct (SA) leads to aqueductal stenosis and hydrocephalus, while disruption of the VZ of telencephalon impairs neurogenesis. We are currently investigating whether grafting of NSCs/neurospheres from normal rats into the CSF of hydrocephalic mutants helps to diminish/repair the outcomes of VZ disruption.

Brain Imaging Studies in Leber's Congenital Amaurosis: New Radiologic Findings Associated with the Complex Trait

PURPOSE: To report the incidence and new findings of abnormal brain imaging studies associated with patients initially diagnosed with Leber's congenital amaurosis (LCA) without definite systemic abnormalities and to determine the need for brain imaging studies in these patients. METHODS: A retrospective review of medical records was performed in 83 patients initially diagnosed as LCA and without definite systemic abnormalities before the age of 6 months in 2 tertiary referral centers. Brain magnetic resonance imaging was performed in 31 of 83 patients (37.3%). RESULTS: Six of 31 patients (19%) had radiologically documented brain abnormalities. Two patients had cerebellar vermis hypoplasia, 1 patient showed an absence of septum pellucidum, 2 subjects showed mild external hydrocephalus, and 1 patient was found to have a small cerebellum. CONCLUSIONS: Approximately one fifth of the LCA patients in whom brain imaging was performed were associated with brain abnormalities, including the absence of septum pellucidum, which has not been documented in the literature. Brain imaging is mandatory in patients primarily diagnosed with LCA, even without definite neurologic or systemic abnormalities.

Causas de hidrocefalia en menores de 13 años de edad / Hydrocephaly in children under 13 years of age

Determinar las patologías que inducen hidrocefalia, frecuencia según sexo y grupo etario, procedimientos y complicaciones en niños menores de 13 años durante las gestiones 2000 – 2004 en el Hospital del Niño Dr. OvidioAliaga Uria. Las causas pueden ser prenatales, genéticas o familiares que se asocia a anomalías cromosómicas, siendo estos factores responsables desconocidos para la mayoría de los autores, infecciosas y/o parasitarias y las de causa posnatal que son losprocesos expansivos e infecciosos.

Importância da avaliação genético-clínica na hidrocefalia / Importance of the clinical genetics evaluation on hydrocephalus

Os objetivos deste estudo foram caracterizar a presença de possíveis quadros de etiologia genética entre portadores de hidrocefalia congênita de etiologia não anteriormente esclarecida e confirmar aqueles com etiologia identificada previamente. A casuística compôs-se de 16 pacientes portadores de hidrocefalia congênita. O protocolo de investigação incluiu anamnese, investigação de história familial, exame clínico-dismorfológico, tomografia computadorizada ou ressonância magnética de sistema nervoso central, radiografia vertebral simples, cariótipo e estudo dismorfológico. Para análise dos resultados, a casuística foi dividida em dois grupos. O Grupo I (3M:6F) caracterizado por indivíduos com hidrocefalia e sinais clínicos inespecíficos; o Grupo II (7M), em que os indivíduos apresentavam hidrocefalia congênita e sinais sugestivos do espectro da doença L1. Orientação genética específica foi possível em 11 casos. Os resultados demonstram a heterogeneidade etiológica envolvida na hidrocefalia, evidenciando a necessidade de avaliação clínico-dismorfológica como instrumento complementar na investigação dessa condição clínica.

Convergencia de los síndromes Vacter-H y Prune Belly / Convergence of the Vacter-H and Prune Belly syndromes

Se informa el caso clinicopatológico de un niño pretérmino que presentó anomalías de los síndromes prune belly y VACTERL con hidrocefalia sin antecedentes consanguíneos. En la autopsia se encontró facies de Potter, orejas de implantación baja y microtia, abdomen prominente, arteria umbilical única. El corazón presentó canal auriculoventricular común, tronco arterial común, foramen oval abierto, pulmón derecho unilobular y el derecho trilobular. El intestino delgado mostró divertículo de Meckel. Había malformación anorrectal alta. Los riñones tenían enfermedad glomeruloquística, dilatación de cálices y pelvis renal, los ureteros estaban dilatados con presencia de una valva en el uretero izquierdo, la vejiga estaba aumentada de tamaño y dilatación del uraco, hipoplasia de la próstata y estenosis de la uretra, criptorquidia bilateral, displasia y alteración del número de vértebras y craneosinostosis. Había hidrocefalia y agenesia del septum pellucidum. Las alteraciones que originaron obstrucción urinaria pudieron ser producidas en etapas tempranas del desarrollo embrionario coincidiendo anomalías del síndrome VACTERL-H y prune belly. En la literatura revisada no encontramos una descripción semejante.

Unilateral hydrocephalus in paediatric patients, a trial of endoscopic fenestration.

Two uncommon cases of unilateral, asymmetrical hydrocephalus secondary to membranous occlusion of foramen of monro are described. Both the cases presented with clinical features of raised intracranial pressure and their cranial computerized scans (CT) revealed asymmetrical dilatation of lateral ventricles with displacement of septum pellucidum towards the side of smaller ventricle. Neuroendoscopic fenestration of septum pellucidum and foramen of monro was tried in both the cases, which remained successful in first, while the second case required unilateral ventriculoperitoneal shunt, due to failed endoscopic negotiation of narrowed foramen of monro and intraoperative bleeding during endoscopic intervention.

Walker-warburg syndrome: reports of two cases

The purpose of this study is to describe two infants that were diagnosed with Walker-Warburg syndrome (WWS), a rare form of congenital muscular dystrophy (CMD). They were studied in their clinical, laboratory, and neuroradiologic features. The index case had a brain magnetic resonance imaging (MRI) and the second patient had a head computerized tomography (CT). In addition, a literature review was performed to describe the main forms of CMD. The index case fulfilled all criteria for WWS. A brain MRI performed at age 4 months served to corroborate the clinical diagnosis, showing severe hydrocephalus, type II lissencephaly, cerebellar vermian aplasia, and a hypoplastic brain stem. The authors were able to establish a retrospective diagnosis of WWS in the index cases's older sister, based upon her clinical picture and head CT report.

Endoscopic third ventriculostomy.

We prospectively studied 8 patients who had an endoscopic third ventriculostomy performed between 1996 and 1997 in Songkhlanagarind Hospital. The surgical technique was described. Seven operations were successful and one operation failed. Success was found in cases of pure aqueductal stenosis, aqueductal stenosis with Dandy Walker malformation, and posterior fossa tumor. In a patient where an endoscopic third ventriculostomy failed, aqueductal stenosis with marked hydrocephalus was found. Marked dilation of the third ventricle could compress the aqueduct of Sylvius. Although there was communicating hydrocephalus, it looked like non-communicating hydrocephalus. To avoid a valvular shunting complication, we suggest performance of an endoscopic third ventriculostomy in selected non-communicating hydrocephalus patients.

Desarrollo psicomotor del hidrocéfalo derivado / Psychomotor development of derivate hydrocephalus

Con el propósito de evaluar el desarrollo psicomotor del paciente Hidrocefálico Derivado, se realizó un estudio de los Hidrocéfalos Derivados desde enero de 1991 hasta diciembre de 1993; cuyo objetivo fue describir su evolución psicomotora después de la intervención (Derivación Ventrículo Peritoneal) utilizando como método el Test de Denver y tomando en cuenta las variables: edad del diagóstico, edad de la intervención, sexo, Desarrollo Motor, Grafias, Praxias. Se obtuvo como conclusión, que los pacientes acuden tardíamente a la consulta de Neurocirugía, trayendo como consecuencia la demora en el tratamiento quirúrgico; aunado al bajo nivel de instrucción de los padres y a la falta de terapia. Especializada, teniendo como resultado final un Desarrollo Psicomotor.

Light & electron microscopic structure of choroid plexus in hydrocephalic guinea pig.

With a view to study the morphological changes, if any, in the choroid plexus in association with hydrocephalus, obstructive hydrocephalus was created in 15 young guinea pigs. The choroid plexus of the control group (n = 16) showed high cuboidal or columnar epithelium. The mitochondria of the choroid plexus ependyma converged towards the apex. Varying concentrations of Golgi complex and rough surfaced endoplasmic reticulum (RER) were noticed in the apical part of the epithelium. Subsurface cistern-like structures and occasional formation of vesicles from the adjacent cells of the epithelium were observed. Basolateral infoldings were numerous and compactly arranged. Most capillaries had their fenestrated part facing the base of the epithelium. Choroid plexus of hydrocephalic guinea pigs showed flattened epithelial cells with less extensive Golgi complex and RER. Mitochondria were found lying parallel to the flattened nucleus. Intercellular spaces were dilated with loosely packed basolateral infoldings. Most of the features observed in the hydrocephalic guinea pig are indicative of reduced activity of the choroid plexus epithelium.

Neurosurgical management of intraventricular haemorrhage in preterm infants

A review of intraventricular haemorrhage [IVH] diagnosed in 103 preterm infants from 1983 to 1993 describes the presenting features and management of this condition. In this 10-year period, 37 infants with IVH developed post-haemorrhagic hydrocephalus [PHH], defined as ventriculomegaly, raised intracranial pressure and increasing head circumference. PHH was treated by external ventricular drainage and/or ventriculo- peritoneal shunting; but other drainage procedures like lumbar punctures and subcutaneous ventricular reservoir were used occasionally. Relative indications, merits and demerits of these various surgical options is discussed and results summarised. High incidence of neuro-developmental handicap and its correlation with the grade of haemorrhage and PHH is emphasized. External ventricular drainage [EVD] was found to be an effective and safe therapy for rapidly progressive PHH and increased intracranial pressure. Ultimate outcome depended mainly on the grade of haemorrhage, severity of PHH and promptness of its neurosurgical management

Morphometry of choroid plexus in hydrocephalic guineapigs.

To study the quantitative changes if any, in different components of the choroid plexus in association with hydrocephalus, young guineapigs were made hydrocephalic by intracisternal injection of kaolin (125 mg/ml). Choroid plexuses of these animals and controls were embedded in durcupan. Using morphometric methods volume and surface area of the choroidal epithelium and interstitial tissue were estimated from 2 microns thick sections. No significant change was observed in the volume of interstitial tissue and surface area of the luminal part of the blood vessels in the hydrocephalic guineapigs. But the volume and surface area of the choroidal epithelium of the hydrocephalic guineapigs showed significant decrease as compared to that of control group, which may be interpreted as decreased activity of the choroidal cells and in turn decreased secretion of CSF in hydrocephalus. This may be secondary to the increased intraventricular pressure associated with hydrocephalus.