What leads to the development of idiopathic scoliosis? This perplexing question, often posed by concerned parents, is precisely what sparked the inception of this work. Although numerous studies have been conducted on this enigmatic condition, most explanations have remained incomplete and distinguishing between primary and secondary causes has proven elusive. The challenge of achieving a comprehensive synthesis is compounded by the fragmented perspectives offered by various medical specialties. Nevertheless, after observing the progression of hundreds of thousands of cases over five decades of clinical practice—many of which were managed without resorting to surgery—a threshold has now been reached. This decision point is grounded in a wealth of accumulated evidence, interpreted through the lens of Ratcliff's diffusion model.  

To begin, let's clarify some definitions: "Etiology" refers to the underlying factors responsible for the onset of idiopathic scoliosis. "Pathogenesis" describes the manner in which this morbid process originates. The term "Pathomechanism" details the sequence of events that lead to structural and functional alterations as a consequence of the pathological process. The term "Etiopathogenesis" is used to encompass both etiology and pathogenesis. In 2013, Burwell introduced the term "Scoliogeny" as an overarching concept to include both "etiologenesis" and "pathomechanism."

To enhance the understanding of the younger generation of sociologists, we'll draw a comparison to a personal computer and its integral parts.

The motherboard of a computer houses a crucial component known as the BIOS, which is an acronym for Basic Input/Output System. This BIOS is tasked with two primary roles. Firstly, it conducts an assessment to ensure that the motherboard components and connected peripherals, such as the keyboard and hard disk, are functioning correctly. Secondly, it is responsible for initiating the operating system. In a manner similar to the BIOS, the extrapyramidal system serves as an autonomous and involuntary network comprised of numerous afferents, autonomous processing centers, and four distinct tracts. These tracts are instrumental in managing functions such as muscle tone. At birth, the extrapyramidal system dominates motor control, yet over time, it is gradually overtaken by the voluntary pyramidal system. However, it continues to play a significant role at the trunk level, where it maintains its importance.

The extrapyramidal system traces its origins back to the rhombencephalon, also known as the hindbrain, which is a feature of primitive vertebrates. This system comprises four primary tracts: firstly, the reticulospinal tract, which emanates from the reticular formation; secondly, the vestibulospinal tract, originating from the vestibular nuclei; thirdly, the rubrospinal tract, which arises from the red nuclei; and lastly, the tectospinal tract, which is derived from the striatum.

The extrapyramidal system plays a crucial role in sustaining the multitude of postures the body adopts, as well as facilitating changes in these postures. The regulation of posture is primarily governed by three key systems: ocular, vestibular, and proprioceptive muscle and joint systems. These systems possess the ability to partially compensate.

There are many radiological classifications. Here we have two curves with a main thoracic curve and a lumbar counter-curve without less rotation. 

More recently in 2019, Marzena Wiernicka confirms poorer postural stability in adolescent girls with scoliosis that is accentuated in right monopodal stance.

In the annals of history, the initial connection between scoliosis and the extrapyramidal system was established by a renowned French physiologist named Jean Pierre Flourens. It was in the year 1824 that Flourens unveiled his pioneering research on pigeons afflicted with scoliosis following the obliteration of the labyrinth. Contrary to his original anticipation of merely inducing deafness, this groundbreaking study paved the way for a deeper understanding of the physiological interplay.

Since Jean Pierre Flourens' pioneering experiments on bipedal pigeons, which developed scoliosis following the disruption of their labyrinthine structures, numerous investigations have underscored the relationship between scoliosis and the postural system. Although it remains uncertain whether this relationship is causal, there is consensus that scoliosis interferes with vertebral proprioception. Building on this understanding, Charles Gabriel Pravaz integrated exercises aimed at invigorating the postural system alongside mechanical interventions for scoliosis correction. This distinctive approach, known as the Lyon Method, has not been embraced by other methodologies. .

In 2023, Shen conducted a study examining three different groups of patients with scoliosis. The first group underwent a regimen that integrated both balance training and curve correction techniques. The second group received treatment focused solely on curve correction. Meanwhile, the third group did not participate in any form of physiotherapy. After a period of six weeks, the outcomes distinctly favored the first group, demonstrating significant improvements, as evidenced by a level 1 randomized controlled trial (RCT). 

The significance of inputs from the extrapyramidal system was highlighted by Sahlstrand as far back as 1979. In a study involving stabilometry, postural sway was measured during caloric labyrinthine stimulation while standing erect in 49 patients aged between 10 and 16 years, all diagnosed with adolescent idiopathic scoliosis. As a comparison group, 32 healthy children of the same age range were evaluated. It was observed that the patients with scoliosis exhibited a greater degree of postural sway when stimulated on the convex side of their curvature, compared to the response on the concave side. Notable differences emerged when comparing scoliotic patients, whether their condition was left or right-sided, with the healthy control group. These findings may be attributed to an asymmetrical sensitivity in the labyrinthine structure or possibly a malfunction within the postural control systems located at the brain stem.

A recently devised assessment to gauge otolith vestibular function, known as the off-vertical axis rotation (OVAR) test—which evaluates imbalances in the otolith system—was conducted on a group of 30 children diagnosed with Idiopathic Scoliosis (IS), alongside 12 control participants, and 3 subjects with congenital scoliosis due to spinal deformities. Among those with IS, a notable 67% displayed significantly elevated directional preponderance values on the OVAR test when juxtaposed with the control group. In contrast, individuals with congenital scoliosis exhibited normal results on the same test. These findings lend credence to the theory that abnormalities in the central otolith vestibular system contribute to an imbalance in the vestibulospinal system, potentially playing a role in the etiology of Idiopathic Scoliosis.

The presence of vestibular-related impairments in these patients is widely recognized; however, it remains uncertain whether a vestibular disorder is the underlying cause of both the scoliotic syndrome and the associated gaze and posture impairments, or whether these behavioral deficiencies arise as a result of the scoliotic deformities. The absence of limb proprioceptive feedback in an aquatic setting serves as the connecting factor between the Xenopus model and human scoliosis, as a similar scenario transpires during fetal development within the womb.

In an effort to investigate a potential vestibular source, researchers conducted an experiment on the frog species Xenopus laevis. During the larval stages, they surgically removed the labyrinthine end organs on the left side. This procedure led to the manifestation of scoliosis, akin to the scoliosis observed in pigeons following a unilateral left labyrinthectomy, as demonstrated by Flourens.

Upon undergoing metamorphosis into young adult frogs, X-ray imaging and three-dimensional reconstructed micro-computed tomographic scans of their skeletons revealed deformities akin to those found in patients with scoliosis. It is the imbalance in the descending reticulospinal and vestibulospinal pathways that indeed leads to the development of scoliosis. This asymmetry in these pathways results in a spinal curvature comparable to idiopathic scoliosis.

This research delves into whether adolescent scoliosis patients experience impairments in feed-forward vestibulomotor control or the mechanisms of sensory reweighting. To gain insights, vestibular-evoked postural responses were assessed using galvanic vestibular stimulation while participants remained standing with their eyes closed and heads facing forward. The study compared the lateral forces exerted under each foot and the lateral displacement of the upper body in adolescents with either mild or severe spine deformation against those of healthy adolescent controls . Notably, adolescents with idiopathic scoliosis exhibited more pronounced lateral displacement and net lateral forces compared to the controls, both during the vestibular stimulation and in the moments following. This suggests that an altered sensory reweighting of vestibular and proprioceptive information affects the balance control in AIS patients during and after such stimulation. Consequently, the onset of scoliosis might be linked to these abnormal sensory reweighting processes, which in turn lead to modified sensorimotor functions. 

Experimental findings suggest that disruptions are not limited to vestibular integration centers alone. Peripheral receptors located along the paravertebral musculature may also be affected.

Two distinct categories of genetically modified mice exhibit changes in the proprioceptive sensors found within their muscles and tendons. Mice that were genetically engineered to lack either type of proprioceptor presented with a similar phenotype, though the symptoms were noticeably milder. These results underscore the crucial role that proprioception plays in preserving spinal alignment.

The intricate tension of the neuro-muscular spindles, characterized by their concave and convex nature, is essential in both qualitative and quantitative aspects of maintaining proper vertebral alignment.

Mice that have been genetically modified to lack proprioceptive receptors exhibit the development of scoliosis during growth. In contrast, mice missing only one of the two types of receptors present a milder form of spinal curvature. Interestingly, this spinal deformity occurs without any prior occurrence of vertebral dysplasia or asymmetry in muscles. It is significant to note that proprioceptive afferents, particularly those associated with the extrapyramidal system, are crucial in preserving the alignment of the spine.

By the age of twelve, the proprioceptive receptors located within the vertebrae of humans have usually reached full maturity. Burwell suggests that scoliosis, particularly its higher prevalence among girls, can be attributed to a delayed maturation of the extrapyramidal system's afferent pathways. This difference of frequency may be linked to the earlier onset of pubertal growth in girls, which typically occurs two years before it does in boys. This phenomenon, known as Neuro-Osseous Timing of Maturation (NOTOM), offers a compelling explanation for the gender disparity observed in the development of scoliosis.

For many years, there have been significant and enduring arguments supporting the idea that the primary cause of scoliosis may be linked to the afferents of the extrapyramidal system. This theory is bolstered by observations such as disruptions in the oculo-vestibular reflex, the enhanced effectiveness of physiotherapy that includes balance training, and the noticeable impairments in postural stability, as well as vestibular and proprioceptive functions in individuals with scoliosis. Additionally, the delayed maturation of the postural system provides insight into why scoliosis is more prevalent in girls.

In addition to these critical factors, it remains essential to study other related concepts. Neuromuscular scoliosis arises from impairments within the central or peripheral pyramidal system; however, scoliosis manifests specifically under circumstances of abrupt asymmetry. The incidence of progressive structural scoliosis in individuals with congenital hemiplegia is marginally greater than the occurrence of idiopathic scoliosis.

In cases of idiopathic scoliosis, there is an absence of any deficits in the pyramidal musculature. It is only after the age of 40 that sarcopenia becomes noticeable. Consequently, any changes to the pyramidal system are considered secondary.

In the 1980s, the genetic understanding of scoliosis sparked significant optimism. It was anticipated that the mapping of the genome would allow us to thoroughly characterize a vast array of diseases. However, this initial excitement gradually gave way to disappointment, prompting a shift in focus toward the study of epigenetics. So, what is the current state of affairs in this field?

The concept of genetics hinges on the understanding of approximately a hundred genetic syndromes that have potential connections with scoliosis. These syndromes have an impact across all chromosomes. As a result, idiopathic scoliosis is not associated with a singular chromosomal anomaly. In his study, Idiopathic scoliosis runs in families. Risenborough discovered that scoliosis occurred in 11.1% of the first-born relatives of individuals diagnosed with idiopathic scoliosis. Furthermore, research on twins revealed a high degree of concordance for scoliosis, with an incidence rate of 92% among monozygotic (identical) twins and 63% among dizygotic (fraternal) twins.  

These two monozygotic twin children, who share an identical environment, undoubtedly have the same brace. However, they do not exhibit the same scoliosis.

Julia is dealing with a condition known as double major scoliosis, whereas Caroline's situation is characterized by a pronounced curvature in her right thoracic region accompanied by minimal rotation in her lower lumbar area.

Léonie and Anais, also monozygoticl twins, present a fascinating case of divergence despite their genetic similarity. Léonie has been diagnosed with thoracolumbar scoliosis, a condition requiring her to wear a corrective brace. In stark contrast, Anais shows no noticeable curvature, leading a life unencumbered by such medical interventions. I frequently cite this illustrative example to highlight the importance of vigilance; yet it also serves as a reminder that progression is not an unavoidable fate.

A total of fifteen genes have been identified to possess SNPs that exhibit a significant correlation with the advancement of progressive AIS; however, none have demonstrated adequate potential for practical clinical use. Contemporary research leans towards epigenetics as a more promising domain for pinpointing elements linked to the progression of AIS, thus providing a compelling basis for continued exploration in this area.  

In 2010, researchers developed a test known as ScolioScore, utilizing around fifty genetic markers. However, this test was found to lack reproducibility across diverse populations, specifically among Caucasian and Asian groups. This inconsistency highlights the conclusion that scoliosis cannot be attributed solely to genetic factors.

Recent publications illustrate a pronounced paradigm shift, now emphasizing the significance of epigenetic biomarkers and the integration of artificial intelligence technologies. In particular, research has revealed that the levels of histone H4—a crucial element of the nucleosome—are reduced in the intervertebral discs of individuals suffering from scoliosis.

A multitude of scholarly articles and publications have established a connection between epigenetics and scoliosis. Below are some illustrative examples: The relationship between nutrition and bodily development. The impact of lifestyle choices and comparative osteopenia. The influence of physical activity on individuals with adolescent idiopathic scoliosis. The correlation between geographic latitude and the occurrence rate of adolescent idiopathic scoliosis. The effect of maternal age and socio-economic conditions. The potential delayed epigenetic consequences of infants exposed to heated indoor swimming pools. The duration and positioning during sleep and their implications.

While epigenetic markers are present, measuring circulating miRNAs serves as a remarkable epigenetic indicator. It is associated with the advancement of the scoliotic curve, yet it does not relate to its origin.

Similar to other chronic conditions, scoliosis cannot be identified through genetic testing. However, exploring the epigenetic factors continues to be beneficial for gaining a deeper insight into the progression of the spinal curvature.

Scoliosis is characterized by a three-dimensional distortion of the spine. Could the root cause of scoliosis be traced back to this particular aspect?  

The irregularity also impacts the rib cage, contributing to its asymmetrical appearance, which serves as a fundamental aspect of clinical scoliometry. This unevenness in the ribs doesn't exclusively stem from rotational factors. It remains a subject of inquiry whether this costal asymmetry is anterior, simultaneous, or posterior to the vertebral deformity.

During the 18th and 19th centuries, the prevailing theory was that scoliosis resulted from the way individuals positioned their bodies. While poor posture might increase the risk of developing Adolescent Idiopathic Scoliosis, it is not the root cause. Instead, scoliosis itself contributes to the appearance of poor posture. Individuals with scoliosis often exhibit uneven shoulders, uneven hips, and a body that leans to one side. However, these asymmetries are not due to bad posture; rather, they are manifestations of the scoliosis condition.

In 2024, Grivas has come close to reaching a definitive conclusion. Through careful examination of school screenings, it has been hypothesized that alterations in vertebral growth associated with the onset of idiopathic scoliosis are not inherent but instead are secondary modifications. The root cause initiating the deformity does not reside within the vertebral bodies themselves. Rather, the distortions observed in these vertebrae are consequential results of uneven forces acting upon them. These forces arise from muscular pressure, growth dynamics, and the influence of gravity.

The detailed examination of school screening reveals that alterations in the rib cage occur before any deformities in the spine.  

In a similar manner, the intervertebral disc undergoes deformation prior to any alteration in the structure of the vertebral body. Consequently, it can be concluded that bone deformation is not an initial occurrence.

Throughout the day, the intervertebral disc undergoes compression, only to rehydrate during the nighttime hours. This movement, where the disc's nucleus shifts towards the area of convexity, serves as the fundamental principle behind the use of hypercorrective night braces for treatment. Nonetheless, these braces address merely one aspect of the broader consequences associated with scoliosis.

During a school screening process, it was observed that among younger girls referred for potential scoliosis—specifically those under the age of 13 exhibiting a trunk rotation angle of seven degrees or more—30% were actually found to either possess a straight spine or to have a spinal curvature with a Cobb angle measuring under 10 degrees. Conversely, in the case of older girls aged between 14 and 18 years who were referred through scoliosis screening, a discernible correlation was identified.

In cases of mild to moderate idiopathic scoliosis, the rotation of the vertebrae is quite limited. Consequently, the distortion of the rib cage is primarily due to uneven rib growth and their resulting deformation, rather than the rotation of the vertebrae, since at this stage, the rotation is not significant.

A tangible clinical application of this notion involves assessing the double costal contour index via profile radiography. When this index exceeds 1.5 at a minimal Cobb angle, it can serve as a predictor for future progression.

Flat backs are also found in fifty percent of cases involving progressive idiopathic scoliosis. Nonetheless, when the curvature is mild, ranging from 10 to 20 degrees, the sagittal plane appears unchanged compared to individuals who do not have scoliosis. Therefore, it is not considered a primary contributor to the development of scoliosis. Despite this, it is crucial to consider flat backs during physiotherapy treatments, as they can influence the progression of the condition in adulthood.

One of the primary implications of the secondary nature of bone deformations is its significant impact on the physiotherapy approach for scoliosis measuring less than 25 degrees. Although curve correction exercises are implemented, they do not address the root cause of idiopathic scoliosis.

A myriad of biological factors have been linked to the development of scoliosis. Extensive research has been conducted on substances such as melatonin, growth hormone, estrogen, calmodulin, and leptin in relation to scoliosis. Machida’s groundbreaking experiment revealed a significant finding: scoliosis developed exclusively in rats that were induced to walk on two legs. This suggests that while hormonal influences play a role, they are secondary to the condition of bipedalism.

In cases of idiopathic scoliosis, the blood levels of melatonin remain within normal ranges. Meanwhile, other hormones exhibit a complex interplay, characterized by their synergistic and opposing influences on bone development, cartilage, and various other bodily functions. This intricate hormonal relationship also interlinks with the advancement of scoliosis, suggesting that such hormonal dynamics are merely secondary contributors to the condition.

Two intrinsic traits of Homo sapiens are closely associated with scoliosis: the growth spurt during puberty and bipedal locomotion. The majority of scoliosis cases tend to exacerbate during the adolescent growth phase, and intriguingly, it is only when rats are altered to walk on two legs that they develop scoliosis following melatonin deprivation by the removal of the pineal gland.  

Nevertheless, these two attributes are clearly of lesser importance. The Duval-Beaupère curve, which illustrates the development of scoliosis during puberty, was initially associated with scoliosis caused by polio. It's important to note that scoliosis does not always commence during adolescence. Additionally, the development of bipedalism, especially in Homo sapiens who have evolved to be more suited for running, could potentially serve as another secondary contributor to the emergence of idiopathic scoliosis.

Alterations in connective tissue have been linked to the development of scoliosis. However, it is important to note that only a specific variant of Ehlers-Danlos syndrome is connected to scoliosis. Consequently, these changes are considered secondary factors rather than primary causes.

Two centuries back, the dismantling of the labyrinth gave rise to the scoliotic pigeon concept and the Lyon Method as a non-invasive approach to treating scoliosis. Our enhanced comprehension of the extrapyramidal system has substantiated this hypothesis. With the optimism generated by genetic research and the meticulous analysis of skeletal deformities, this hypothesis has transformed into a definitive certainty. This examination of the diverse etiological theories of scoliosis now allows us to distinguish the foundational central concept, which resides within the afferent pathways of the extrapyramidal system, akin to a computer's motherboard. Consequently, it is feasible to contemplate specific physiotherapeutic interventions for scoliosis under 20 degrees. In contrast, many of the other etiological theories serve as progressive prognostic indicators that are essential to comprehend in order to more effectively direct the treatment of scoliosis surpassing 20 degrees.