Abstract
Introduction
Type 1 neurofibromatosis is a serious hereditary disease in which mainly skin, nervous, muscular, and bone systems are damaged. In bone systems the most common deformities are thoracic kyphosis and scoliosis. Data for morphological changes in the structural components of spine in neurofibromatosis are scarce. Thus our study aimed to investigate morphological changes in structural components of the spine in NF1 neurofibromatosis.
Methods
Growth plates, intervertebral discs, and fragments of vertebral bodies from deformed and adjacent segments of the spine were obtained from 15 patients aged 10–14 years with scoliosis (Cobb angle 90–120°) caused by neurofibromatosis. Preoperative examination included MRI study of the spine and brain to exclude intracanal masses, and radiographic study of the spine. Patients did not present any neurological symptoms. All children underwent anterior release and interbody fusion. Structural spinal components from children aged 12–14 years collected at forensic autopsy were used as controls. Tissues were investigated by conventional histochemical and ultrastructural methods. The levels of aggrecan and NF1 gene expression were studied with the PCR method.
Results
The study of growth plate and intervertebral disc specimens removed during surgery for scoliosis in neurofibromatosis showed a clear boundary between their convex and concave sides. Both growth plate and intervertebral disc in convex side retain their architectonic and histochemical characteristics. The concave side of the growth plate is presented by small chondroblasts densely spaced without a definite orientation and surrounded by homogeneous matrix, which is made up of chondroitin sulphates. These embryonic-type chondroblasts are poorly differentiated. Chondroblasts proliferate beyond the growth plate. Proliferating cells invade into vertebral body and are bordered by thin bone lamellae, causing the scalloping of vertebral body as a radiological symptom of the pathology. Changes occurring in the intervertebral disc are of considerable interest. Concave-side disc is characterised by isolated proliferation zones containing poorly differentiated chondroblasts and fibroblasts, and neurinoma-like masses. Bone trabeculae inside a concave-side vertebra are passing the stage of osteogenesis imperfecta. Detected morphological changes in spinal structures are consistent with findings of Stevenson, who registered cartilage and bone deficiencies in animal model (mice with NF1 genemutation). Thus, morphological studies testify to structural disorder in concave side of the growth plate, but unchanged regularities and stages of chondroblast differentiation and adequate osteogenesis in the convex side. NF1 gene regulates the growth, differentiation, and proliferation of chondroblasts at the early stage of embryogenesis. Gene inactivation at a somite stage results in altered development of definitive spinal structures. Continued growth with adequate proliferation, differentiation, osteogenesis, and topochemical characteristics occurs in the convex-side growth plate, and growth disorder in the concave-side part with continued load cause growth asymmetry and development of spinal deformity. Scoliosis associated with neurofibromatosis is notable for deformity progression and pseudoarthrosis development after surgery. Deformity progression (modulation) should be considered in connection with disorder in osteogenic potency of osteoblasts.
Conclusions
The causal factor of spinal deformity development in NF1 neurofibromatosis is NF1 gene mutation. Inactivation of NF1 gene results in disorder in chondrogenesis and osteogenesis within structurally altered zones. A continued load causes development of scoliotic spinal deformity.
