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.

Estenosis acueductal en acondroplasia: a propósito de un caso / Aqueductal stenosis in achondroplasia: report of a case

Achondroplasia is the most frequent cause of disproportionate short stature. Characterized by abnormal growth of long bones, it renders a short-limbed individual of normal intelligence. A serious potential complication is spinal compression, which can happen at any level but is particularly common at the craniocervical junction. It can cause important morbility during the first few years of life, including sudden death. We present a 22-month-old patient diagnosed with achondroplasia, who developed aqueductal stenosis with symptomatic spinal cord compression, diagnosed during a routine consultation, requiring decompressive surgery with excellent results.

La acondroplasia es la condición asociada a talla baja desproporcionada más frecuente, caracterizada por un crecimiento óseo anormal, que resulta en talla baja con extremidades cortas e inteligencia normal. Una de las complicaciones más habituales es la compresión medular, que puede ocurrir a cualquier nivel, siendo más frecuente en la unión cráneo cervical, generando alta morbimortalidad en los primeros años de vida, principalmente por muerte súbita. Presentamos una paciente de 1 año 10 meses con diagnóstico precoz de acondroplasia, que presentó en su evolución estenosis acueductal con compresión medular, sintomática, pesquisada en control rutinario, que requirió cirugía descompresiva con buena evolución posterior.

Central neurocytomas of uncommon locations: report of two cases / Localizações incomuns do neurocitoma central: relato de dois casos

We report two patients with central neurocytomas at an uncommon location in the brain. The first, a 58-year-old man presenting with signs and symptoms of increased intracranial pressure, had a tumor located at the pineal region. The second, a 21-year-old woman with tumor in the aqueductal region had worsening migraine-like headaches and diplopia. Both patients had obstructive hydrocephalus treated by neuroendoscopic third ventriculostomy and biopsy of the tumors. No additional treatment was done. We conclude that neurocytomas should be considered in the differential diagnosis of tumors located in the pineal and aqueductal regions.

Relatamos dois pacientes com neurocitoma central com localização incomum no sistema nervoso central. O primeiro, 58 anos, masculino, apresentava sinais e sintomas de hipertensão intracraniana, tinha um tumor na região da pineal. O segundo, feminino, 21 anos, tinha um tumor na região do aqueduto de Sylvius e apresentava cefaléia migranosa progressiva e diplopia. Ambos apresentavam hidrocefalia obstrutiva tratada com terceiroventriculostomia endoscópica e biópsia da lesão. Não foi feito tratamento adicional. Concluimos que os neurocitomas devem ser considerados no diagnóstico diferencial de tumores localizados na região da pineal e do aqueduto.

Subacute sclerosing panencephalitis in a case of aqueductal stenosis.

A 14-year-old boy presented with history of deterioration of scholastic performance, altered behaviour, difficulty in walking and repeated falls since last 2-3 months. He had history of delayed milestones and at 11 months developed febrile rashes. On investigations, MRI showed compensated hydrocephalus with aqueductal stenosis. EEG suggested subacute sclerosing panencephalitis (SSPE). CSF was positive for measles antibody titre. This case of aqueductal stenosis with SSPE is very interesting for its diagnostic dilemma.

Congenital hydrocephalus due to aqueductal stal stenosis of probable autosomal recessive inheritance

Hereditary stenosis of the aqueduct of Sylvius is known to be transmitted as an X-linked recessive trait, thus affecting only the male offspring. We describe a family of consanguineous marriage where 2 sons and 2 daughters were afflicted with congenital hydrocephalus associated with stenosis of aqueduct of Sylvius. The pattern of the disease in this family is consistent with autosomal recessive inheritance. The authors of this communication are not aware of any literature reporting a similar mode of inheritance regarding this condition. Perhaps this discordant genetic mode of inheritance could have been caused by the consanguinity between the parents

Congenital hydrocephalus due to aqueductal stenosis of probable autosomal recessive inheritance

Hereditary stenosis of the aqueduct of Sylvius is known to be transmitted as an X-linked recessive trait, thus affecting only the male offspring. We describe a family of consanguineous marriage where 2 sons and 2 daughters were afflicted with congenital hydrocephalus associated with stenosis of aqueduct of Sylvius. The pattern of the disease in this family is consistent with autosomal recessive inheritance. The authors of this communication are not aware of any literature reporting a similar mode of inheritance regarding this condition. Perhaps this discordant genetic mode of inheritance could have been caused by the consanguinity between the parents

Diagnóstico diferencial en la estenosis del acueducto de Silvio en el adulto / Differential diagnosis of Sylvius aqueduct stenosis in the adult

El diagnóstico de la estenosis del acueducto de Silvio en el adulto se ha facilitado con el advenimiento de la tomografía axial computada (TAC). Los datos tomográficos son la dilatación de los ventrículos laterales y del tercer ventrículo con un IV ventrículo normal. En el presente trabajo se reporta la experiencia obtenida en el Servicio de Neurología del Hospital Universitario en Monterrey, con diez casos inicialmente diagnosticados por clínica y TAC como estenosis del acueducto. El diagnóstico definitivo se estableció en seis (concordando con el diagnóstico de ingreso), y en cuatro se demostraron otras etiologías como causa de este síndrome. Es importante la realización de TAC asociada a ventriculografía (VG) mediante microtrepano frontal lo cual nos permite definir otras posibles causas de obstrucción del acueducto. Algunas etiologías son: Cisticero en la porción distal del tercer ventrículo (caso 7) neoplásica periacueductal (caso 8) y cisticercos múltiples intraventriculares (caso 10), todos éstos sólo pudieron ser establecidos mediante la V.G. Se revisan los patrones de presentación clínica, enfatizándose la utilidad que la VG asociada a TAC proporcionan para la realización del diagnóstico definitivo de este síndrome, lo cual es importante en el manejo y pronóstico de estos pacientes