A musculoskeletal model of low grade connective tissue inflammation in patients with thyroid associated ophthalmopathy (TAO): the WOMED concept of lateral tension and its general implications in disease

Abstract

Background: Low level connective tissue inflammation has been proposed to play a role in thyroid associated ophthalmopathy (TAO). The aim of this study was to investigate this postulate by a musculoskeletal approach together with biochemical parameters.

Methods: 13 patients with TAO and 16 controls were examined. Erythrocyte levels of Zn, Cu, Ca2+, Mg, and Fe were determined. The musculoskeletal evaluation included observational data on body posture with emphasis on the orbit-head region. The angular foot position in the frontal plane was quantified following gait observation. The axial orientation of the legs and feet was evaluated in an unloaded supine position. Functional propioceptive tests based on stretch stimuli were done by using foot inversion and foot rotation.

Results: Alterations in the control group included neck tilt in 3 cases, asymmetrical foot angle during gait in 2, and a reaction to foot inversion in 5 cases. TAO patients presented facial asymmetry with displaced eye fissure inclination (mean 9.1 degrees) as well as tilted head-on-neck position (mean 5.7 degrees). A further asymmetry feature was external rotation of the legs and feet (mean 27 degrees). Both foot inversion as well as foot rotation induced a condition of neuromuscular deficit. This condition could be regulated by gentle acupressure either on the lateral abdomen or the lateral ankle at the acupuncture points gall bladder 26 or bladder 62, respectively. In 5 patients, foot rotation produced a phenomenon of moving toes in the contra lateral foot. In addition foot rotation was accompanied by an audible tendon snapping. Lower erythrocyte Zn levels and altered correlations between Ca2+, Mg, and Fe were found in TAO.

Conclusion: This whole body observational study has revealed axial deviations and body asymmetry as well as the phenomenon of moving toes in TAO. The most common finding was an arch-like displacement of the body, i.e. eccentric position, with foot inversion and head tilt to the contra lateral side and tendon snapping. We propose that eccentric muscle action over time can be the basis for a low grade inflammatory condition. The general implications of this model and its relations to Zn and Se will be discussed.

Figure 1

Description of the axis definitions used in the study. The positive x direction was the forward orientation, the positive y direction was the rightward orientation, and the positive z direction was the upward orientation

Figure 2

A TAO patient showing moderate changes in facial symmetry. Misalignments of the eyes on the orbit and of the orbit on the head are noted.

Figure 3

A TAO patient showing complex changes of facial symmetry. These include Y+ changes in the head on neck position, of the orbital axes as well as on the alignment of the eyes on the orbit.

Figure 4

TAO patient showing left rotation the orbits and head as seen by photographic documentation taken from above.

Figure 5

Description of the foot orientation patterns observed during gait. The left panel shows a symmetrical gait. The middle panel shows a lateral foot deviation. The right panel signalizes a rotating, semicircular pattern of foot advancement.

Figure 6

Description of the changes in foot alignment while lying supine in an unloaded position. The left panel shows a symmetrical position. The middle panel shows a slight displacement of the Y axis. The right panel shows a more pronounced displacement of the foot in the Y axis corresponding to inversion.

Figure 7

Description of the foot rotation test by which several muscle groups are activated. Besides the muscle activation propioceptive stimuli arise from skin and tendon stretching.

Figure 8

Schematic representation of the head on neck on trunk postural changes showing head rotation in a Y+ direction. Besides this rotation, lateral head tilting can also be present.

Figure 9

Schematic representation of the pitch changes of the head on neck position.

Figure 10

Schematic summary of the WOMED concept of lateral tension. The four panels describe the graded development of lateral tension. Panel A shows the symmetrical body position. Panel B includes only Y+ tilting of the head. Panel C includes Y+ tilting, alteration of the orbits and slight eccentric position of the leg and foot. Panel D shows the complex pattern with head, orbit, face and lower limb asymmetry. We propose that in this stage eccentric muscle action will induce low grade inflammation.

Figure 11

Simulated patient photography demonstrating the lateral tension concept. The basic elements of the model are included.

Figure 12

Image fusion of CT and scintigraphic data showing diffuse Octreotide uptake in the lower limbs of a patient with TAO. Octreotide uptake represents inflammatory activity. Taken from [49]. Each reconstruction plane is labeled in the upper left corner of the image. The right lower image is an anatomical reconstruction of the surface of the leg.

Figure 13

Graphical summary of relevant scientific data related to the effects of eccentric muscle action. The images recollect physiological data as well as nutritional and endocrine aspects. Emphasis is put on the roles of Zn and Se.

Figure 14

Graphical summary of relevant scientific data related to Ca regulation. Ca regulation has been suggested to be important in TAO. This assumption is based on the finding of antibodies directed against calsequestrin [40,370]. Interactions with Zn and Se are included.

Figure 15

Metabolic imaging using whole body ¹⁸F-Fluorodeoxyglucose PET and CT. Note the metabolic activity on the lateral side of the left lower limb as well as on the right ankle. The area around the ankle corresponds to the Shen mai acupuncture point which has been evaluated in our study. Shank muscles are commonly more active in locomotion. The image was provided courteously by Dr David Townsend, University of Tennessee [165].

Figure 16

Metabolic imaging using ¹⁸F-Fluorodeoxyglucose (18F-FDG) showing metabolic activity in the lateral abdomen (dark areas). These areas are located around the Dai mai point which has been evaluated in our study. The accompanying CT images shows a clear deviation of the body axis at the level of the trunk. The images are reproduced with kind permission of the Society of Nuclear Medicine [166].

Figure 17

Graphical summary of scientific data related to inflammation as it can be applied in TAO and in metabolic disorders including insulin resistance. Interactions with IL-6 and Se are depicted.

Figure 18

Abbridged representation of the WOMED concept of lateral tension in relation to inflammation and daily low level stressors. Further details can be extracted from figures 13, 14 and 17.