Pathogenesis of adolescent idiopathic scoliosis in girls - a double neuro-osseous theory involving disharmony between two nervous systems, somatic and autonomic expressed in the spine and trunk: possible dependency on sympathetic nervous system and hormones with implications for medical therapy

Abstract

Anthropometric data from three groups of adolescent girls - preoperative adolescent idiopathic scoliosis (AIS), screened for scoliosis and normals were analysed by comparing skeletal data between higher and lower body mass index subsets. Unexpected findings for each of skeletal maturation, asymmetries and overgrowth are not explained by prevailing theories of AIS pathogenesis. A speculative pathogenetic theory for girls is formulated after surveying evidence including: (1) the thoracospinal concept for right thoracic AIS in girls; (2) the new neuroskeletal biology relating the sympathetic nervous system to bone formation/resorption and bone growth; (3) white adipose tissue storing triglycerides and the adiposity hormone leptin which functions as satiety hormone and sentinel of energy balance to the hypothalamus for long-term adiposity; and (4) central leptin resistance in obesity and possibly in healthy females. The new theory states that AIS in girls results from developmental disharmony expressed in spine and trunk between autonomic and somatic nervous systems. The autonomic component of this double neuro-osseous theory for AIS pathogenesis in girls involves selectively increased sensitivity of the hypothalamus to circulating leptin (genetically-determined up-regulation possibly involving inhibitory or sensitizing intracellular molecules, such as SOC3, PTP-1B and SH2B1 respectively), with asymmetry as an adverse response (hormesis); this asymmetry is routed bilaterally via the sympathetic nervous system to the growing axial skeleton where it may initiate the scoliosis deformity (leptin-hypothalamic-sympathetic nervous system concept = LHS concept). In some younger preoperative AIS girls, the hypothalamic up-regulation to circulating leptin also involves the somatotropic (growth hormone/IGF) axis which exaggerates the sympathetically-induced asymmetric skeletal effects and contributes to curve progression, a concept with therapeutic implications. In the somatic nervous system, dysfunction of a postural mechanism involving the CNS body schema fails to control, or may induce, the spinal deformity of AIS in girls (escalator concept). Biomechanical factors affecting ribs and/or vertebrae and spinal cord during growth may localize AIS to the thoracic spine and contribute to sagittal spinal shape alterations. The developmental disharmony in spine and trunk is compounded by any osteopenia, biomechanical spinal growth modulation, disc degeneration and platelet calmodulin dysfunction. Methods for testing the theory are outlined. Implications are discussed for neuroendocrine dysfunctions, osteopontin, sympathoactivation, medical therapy, Rett and Prader-Willi syndromes, infantile idiopathic scoliosis, and human evolution. AIS pathogenesis in girls is predicated on two putative normal mechanisms involved in trunk growth, each acquired in evolution and unique to humans.

Association of GPR126 gene polymorphism with adolescent idiopathic scoliosis in Chinese populations

“…Several morphological studies have reported that individuals with AIS have imbalanced and faster longitudinal growth of the vertebral bodies, as well as extraspinal skeletal length asymmetries [10][11][12]. A recent study reported that GPR126-null mice have limb posture abnormalities and growth failure [13].…”

Swimming and Spinal Deformities: A Cross-Sectional Study

“…6 According to many authors, gravity plays a role in the development and progression of scoliosis. 7 Even in ancient times, Hippocrates attempted hanging patients with scoliosis to counteract the negative effect of spinal load or to place the spine in traction using specific tools, the Hippocratic board and the Hippocratic ladder. 8 Despite these theories, however, as far as we know no data have been published to support the efficacy of swimming as a specific scoliosis treatment.…”

Physical Therapy for Adolescents with Idiopathic Scoliosis

“…We have recently defined idiopathic scoliosis as a www.intechopen.com multi-factorial three-dimensional deformity of the spine and the trunk, which appears and can progress during any of the rapid periods of growth in apparently healthy children. The aetiology is unknown but some models explain how idiopathic scoliosis develops and progresses (Burwell, 2009). The basic scoliosis deformity is classically described as a lateral deviation of the spine associated with axial rotation, however, it can be better defined as a combination of torsional regions separated by junctional zones, each region formed by a variable number of vertebrae in extension (or lordosis) deviated and rotated to the same side (Dubousset 1992).…”