Neurosurgical embryology. Part 6: The principal models that can be used in developmental biology

To study the mechanisms controlling embryonic development, experimental analyses must be performed on animal models. There are different species that are currently used as models in developmental biology. In invertebrates, drosophila remains a very useful model thanks to its rapid development and to the extensive study of genes involved in the control of its development. C. elegans has been extensively used because of its simplicity due to the total restricted number of adult cells in this species. In vertebrates, amphibians remain a very useful model with the extensive analysis of Xenopus laevis. The zebrafish is now a widely used model because of its genetic analysis. Birds are still used for the accessibility of their embryo allowing experimental procedures to be performed in ovo. The mouse is now very widely used because it is possible to obtain transgenic mice to study both loss or gain of gene function.     

Neurosurgical embryology. Part 7: Development of the spinal cord, the spine and the posterior fossa

The spinal cord arises from the most caudal domain of the neural tube whereas the vertebrae develop from the para-axial mesoderm (namely the somites). The development of the spinal cord and the vertebrae is so intimately linked that it is more convenient to present it in the same chapter. The neural tube is formed from the neural plate during neurulation. This tube is submitted to a double gradient of diffusible molecules that lead to the ventro-dorsal polarization of the tube. This polarization is figured as the emergence of sub-domains that contain progenitors engaged in a specific lineage. Axial organs induce the dissociation of the somites, giving rise to the dermatome, myotome and sclerotome. Vertebrae derive from the sclerotome after the so-called resegmentation of the somites. During this process, a caudal hemi-somite is associated with the rostral hemi-somite of the next caudal somite to differentiate into the vertebra. The occipital bone forms the major part of the walls of the posterior fossa. This bone develops from the para-axial mesoderm for its sub-tentorial part whereas its sus-tentorial derives from neural crest cells.     

Neurosurgical Embryology. Part 2: Recent data on normal and pathological development of the cortex

Understanding how the cortex develops has gained very important new data thanks to both experimental and clinical studies. Experimental studies have shown that: --neurons are generated in the ventricular zone by asymmetric mitoses; --the first cortical region to differentiate is the so-called pre-plate that plays a major role in the control of neuroblasts migration; --neuroblasts arise according to an inside-outside gradient; they migrate either along the processes of radial cells or according to a new type of non radial migration; --all the cortical neurons are not generated by the dorsal telencephalon; some of these neurons derive from the basal telencephalon; --neuroblasts acquire their specificity during their way to the cortical plate. There are several genetic syndromes leading to a malformation of the cortex. Classic lissencephaly is essentially due to mutations of the LIS1 or the DCX genes. These genes code for proteins that are involved in cytoskeleton functions. Reelin is responsible for a human syndrome associating pachygyria and cerebellar hypotrophy. Subventricular heterotopia can be X- inherited and are due to a mutation of the gene coding for filamin 1.     

Neurosurgical intervention for Parkinson's disease: an update.

For patients with advanced Parkinson's disease who do not respond to levodopa anymore, neurosurgical intervention is the only option. Cell transplantation has not met expectations as yet. Deep brain stimulation is gaining ground and currently seems to be the most efficient, flexible, and safe procedure.     

Chordal plication and free edge remodeling for mitral anterior leaflet prolapse repair: 8-year follow-up.

BACKGROUND: Chordal suture plication and free edge remodeling represent a personal technique for the repair of anterior leaflet prolapse. We report the results of an 8-year experience. METHODS: Sixty-one patients with degenerative mitral regurgitation caused by prolapse of the anterior leaflet (11) or both leaflets (50) underwent anterior leaflet prolapse repair. Twenty patients who had associated cardiac procedures are included. RESULTS: There were two perioperative deaths. Postoperative mitral regurgitation fell to 0.4 +/- 0.7 versus 3.7 +/- 0.4 preoperative (p < 0.0001). Mean follow-up was 40.5 months. There were 3 late deaths and 3 mitral reoperations (1 of 3 repairs, 2 of 3 replacements). Thromboembolism and endocarditis occurred in 1 patient each. Actuarial overall survival, freedom from cardiac death, and freedom from mitral reoperation at 92 months were 85.1% +/- 7.9%, 88.9% +/- 7.7%, and 94.6% +/- 3.0%, respectively. CONCLUSIONS: Our technique of anterior leaflet prolapse repair appears effective, safe, and durable at mid- to long-term follow-up, and may be used in the presence of extensive disease of both leaflets.     

The embryology and surgical management of gastroschisis.

Thirteen cases of gastroschisis are presented and a reduction in the operative mortality to 15 per cent is recorded. The aetiology of the condition is discussed and the opinion expressed that it represents the result of an intra-uterine rupture of an incarcerated "hernia into the cord" rather than any specific failure of development of the abdominal wall musculature. Early skin closure and the creation of a ventral hernia remain the surgical treatment of choice, but it is recognized that the use of a prosthetic sac may occasionally be necessary. Infection is not the most important single factor influencing mortality, and the prolonged administration of prophylactic antibiotics is justified on this basis. Skilled management of the protracted ileus is essential. In view of the low incidence of serious coexistent malformations the children who survive the initial operation can be offered the prospect of a life of normal duration and quality.     

Impaired angiogenesis, early callus formation, and late stage remodeling in fracture healing of osteopontin-deficient mice.

OPN is an ECM protein with diverse localization and functionality. The role of OPN during fracture healing was examined using wildtype and OPN(-/-) mice. Results showed that OPN plays an important role in regulation of angiogenesis, callus formation, and mechanical strength in early stages of healing and facilitates late stage bone remodeling and ECM organization. INTRODUCTION: Osteopontin (OPN) is an extracellular matrix (ECM) protein with diverse localization and functionality that has been reported to play a regulatory role in both angiogenesis and osteoclastic bone remodeling, two vital processes for normal bone healing. MATERIALS AND METHODS: Bone repair in wildtype and OPN(-/-) mice was studied using a femoral fracture model. microCT was used for quantitative angiographic measurements at 7 and 14 days and to assess callus size and mineralization at 7, 14, 28, and 56 days. Biomechanical testing was performed on intact bones and on fracture specimens at 14, 28, and 56 days. Histology and quantitative RT-PCR were used to evaluate cellular functions related to ECM formation and bone remodeling. RESULTS: OPN deficiency was validated in the OPN(-/-) mice, which generally displayed normal levels of related ECM proteins. Intact OPN(-/-) bones displayed increased elastic modulus but decreased strength and ductility. Fracture neovascularization was reduced at 7 but not 14 days in OPN(-/-) mice. OPN(-/-) mice exhibited smaller fracture calluses at 7 and 14 days, as well as lower maximum torque and work to failure. At 28 days, OPN(-/-) mice had normal callus size but a persistent reduction in maximum torque and work to failure. Osteoclast differentiation occurred normally, but mature osteoclasts displayed reduced functionality, decreasing late stage remodeling in OPN(-/-) mice. Thus, at 56 days, OPN(-/-) fractures possessed increased callus volume, increased mechanical stiffness, and altered collagen fiber organization. CONCLUSIONS: This study showed multiple, stage-dependent roles of OPN during fracture healing. We conclude that OPN deficiency alters the functionality of multiple cell types, resulting in delayed early vascularization, altered matrix organization and late remodeling, and reduced biomechanical properties. These findings contribute to an improved understanding of the role of OPN in vivo and provide new insight into mechanistic control of vascularization and bone regeneration during fracture repair.     

Neurosurgical treatment of spasticity: selective posterior rhizotomy and intrathecal baclofen.

The pathophysiology of spasticity and the history of posterior rhizotomies are reviewed. The rationale for selective posterior rhizotomies is that electrical stimulation identifies afferent posterior rootlets that terminate on relatively uninhibited alpha motoneurons; if these uninhibited rootlets are divided, spasticity can be alleviated without loss of other posterior root functions. Indications, technique, and results of selective posterior rhizotomies are presented. The use of continuous intrathecal baclofen (CITB) is summarized. CITB at doses of approximately 300 micrograms/day consistently reduces lower extremity spasticity and diminishes or alleviates muscle spasms in adults with spasticity of spinal origin. Single doses of intrathecal baclofen significantly decrease lower extremity muscle tone in children with cerebral palsy, and the effects can be maintained in these patients by CITB infusions which diminish muscle tone not only in the lower extremities, but in the upper extremities as well. CITB is best accomplished via an externally programmable pump that allows titration of the daily dose to attain the desired reduction in spasticity. Factors influencing the decision for rhizotomy or CITB are presented.