The role of the autonomic nervous system in the etiology of idiopathic scoliosis: prospective electron microscopic and morphometric study

Repko, Martin; Horký, Drahomír; Krbec, Martin; Chaloupka, Richard; Brichtová, Eva; Lauschová, Irena

doi:10.1007/s00381-007-0555-7

Cited by 10 publications

(10 citation statements)

References 15 publications

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“…Subsequent experimental studies [61] provided evidence for the correction of experimentally-induced scoliosis consistent with the pathogenetic conclusions. The thoracospinal concept is supported by recent studies on breast size [183], vascular [184,185] and peripheral nerve [186] findings. It does not encompass evidence relating to the new neuroskeletal biology, energy homeostasis, or white adipose tissue which is central to the regulation of energy balance by adipokines, particularly leptin, hormones of the digestive system and metabolites, particularly glucose (Figure 8).…”

Section: Scientific Basis Of Leptin-hypothalamic-sympathetic Nervous mentioning

confidence: 87%

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

et al. 2009

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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.

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Section: Scientific Basis Of Leptin-hypothalamic-sympathetic Nervous mentioning

confidence: 87%

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

et al. 2009

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“…12. Whether spinal nerve roots may develop 'insufficiency' and, with it, left-right asymmetries to induce spinal root neuro-osseous tethers [[ 23 , 91 ] Moderator see [ 92 ]].…”

Section: Introductionmentioning

confidence: 99%

Relative shortening and functional tethering of spinal cord in adolescent scoliosis – Result of asynchronous neuro-osseous growth, summary of an electronic focus group debate of the IBSE

Chu

Lam

et al. 2008

Scoliosis

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There is no generally accepted scientific theory for the causes of adolescent idiopathic scoliosis (AIS). As part of its mission to widen understanding of scoliosis etiology, the International Federated Body on Scoliosis Etiology (IBSE) introduced the electronic focus group (EFG) as a means of increasing debate on knowledge of important topics. This has been designated as an online Delphi discussion. The Statement for this debate was written by Dr WCW Chu and colleagues who examine the spinal cord to vertebral growth interaction during adolescence in scoliosis. Using the multi-planar reconstruction technique of magnetic resonance imaging they investigated the relative length of spinal cord to vertebral column including ratios in 28 girls with AIS (mainly thoracic or double major curves) and 14 age-matched normal girls. Also evaluated were cerebellar tonsillar position, somatosensory evoked potentials (SSEPs), and clinical neurological examination. In severe AIS compared with normal controls, the vertebral column is significantly longer without detectable spinal cord lengthening. They speculate that anterior spinal column overgrowth relative to a normal length spinal cord exerts a stretching tethering force between the two ends, cranially and caudally leading to the initiation and progression of thoracic AIS. They support and develop the Roth-Porter concept of uncoupled neuro-osseous growth in the pathogenesis of AIS which now they prefer to term 'asynchronous neuro-osseous growth'. Morphological evidence about the curve apex suggests that the spinal cord is also affected, and a 'double pathology' is suggested. AIS is viewed as a disorder with a wide spectrum and a common neuroanatomical abnormality namely, a spinal cord of normal length but short relative to an abnormally lengthened anterior vertebral column. Neuroanatomical changes and/or abnormal neural function may be expressed only in severe cases. This asynchronous neuro-osseous growth concept is regarded as one component of a larger concept. The other component relates to the brain and cranium of AIS subjects because abnormalities have been found in brain (infratentorial and supratentorial) and skull (vault and base). The possible relevance of systemic melatonin-signaling pathway dysfunction, platelet calmodulin levels and putative vertebral vascular biology to the asynchronous neuro-osseous growth concept is discussed. A biomechanical model to test the spinal component of the concept is in hand. There is no published research on the biomechanical properties of the spinal cord for scoliosis specimens. Such research on normal spinal cords includes movements (kinematics), stress-strain responses to uniaxial loading, and anterior forces created by the stretched cord in forward flexion that may alter sagittal spinal shape during adolescent growth. The asynchronous neuro-osseous growth concept for the spine evokes controversy. Dr Chu and colleagues respond to five other concepts of pathogenesis for AIS and suggest that relative anterior spinal overgrowt...

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“…A longitudinal study of anterior chest wall blood supply of girls with progressive right thoracic (RT) AIS, supports the view that RT AIS in females is associated with a disturbance in the autonomic nervous system regulating blood flow to the anterior chest wall [77,78]. The thoraco-spinal concept is supported by recent peripheral nerve studies [79]. …”

Section: Discussionmentioning

confidence: 77%

“…• disturbance in the autonomic nervous system regulating blood flow to the anterior chest wall in girls with right thoracic AIS [76-79] – unless the sympathetic nervous system also has Gi-signaling defect, or induces a Gi-signaling defect in growth plates and bone (see below).…”

Section: Discussionmentioning

confidence: 99%

Changing a "progressive" factor into a "corrective" factor: the effect of intervertebral disc modulation in treatment of idiopathic scoliosis

et al. 2009

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BMI is a surrogate measure for body fat and circulating leptin levels. The finding that girls with relatively lower BMI have significantly later menarche, and a significant excess of TAs, suggests a relation to energy homeostasis through the hypothalamus. The hypothesis we suggest for the pathogenesis of severe TA in girls and boys has the same mechanism as that proposed recently for AIS girls, namely: severe TAs are initiated by a genetically-determined selectively increased hypothalamic sensitivity (up-regulation, i.e. increased sensitivity) to leptin with asymmetry as an adverse response to stress (hormesis), mediated bilaterally mainly to the growing trunk via the sympathetic nervous system (leptin-hypothalamic-sympathetic nervous system (LHS) concept). The putative autonomic dysfunction is thought to be increased by any lower circulating leptin levels associated with relatively lower BMIs. Sympathetic nervous system activation with asymmetry leads to asymmetries in ribs and/or vertebrae producing severe TA when beyond the capacity of postural mechanisms of the somatic nervous system to control the shape distortion of the trunk. A test of this hypothesis testing skin sympathetic responses, as in the Rett syndrome, is suggested.

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The role of the autonomic nervous system in the etiology of idiopathic scoliosis: prospective electron microscopic and morphometric study

Abstract: There are significant morphologic changes in spinal autonomic nervous structures in scoliotic patients. These findings can help us in the search for the etiology of scoliosis.

Cited by 10 publications

References 15 publications

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

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

Relative shortening and functional tethering of spinal cord in adolescent scoliosis – Result of asynchronous neuro-osseous growth, summary of an electronic focus group debate of the IBSE

Changing a "progressive" factor into a "corrective" factor: the effect of intervertebral disc modulation in treatment of idiopathic scoliosis

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