The aim of this study was to evaluate the effects of different wrist positions (neutral, flexion, extension, and ulnar deviation) on median nerve morphology in patients with generalized joint hypermobility (GJH) using ultrasonography and to compare them with healthy controls.

The investigators' hypothesis is that the deformability of the median nerve in response to active maximal wrist flexion, extension, or ulnar deviation may be increased in patients with GJH

This prospective cross-sectional study will include 18 female patients diagnosed with GJH (Beighton score ≥5) and 18 healthy volunteers with similar age, gender, and body mass index. Both wrists of all participants (total of 72 wrists) will be evaluated using ultrasonography. Images of the median nerve will be obtained in neutral position, active maximal flexion, extension, and ulnar deviation. The cross-sectional area and perimeter of the median nerve will be measured in each position, and circularity will be calculated. Deformation ratios will be determined.

Ultrasonographic Evaluation

Ultrasonographic evaluation was performed using a Mindray DC-7 ultrasound device. The ultrasonographic imaging of participants was performed while the shoulder was in neutral position with the forearm resting on a fixed surface in supination, and with the patient sitting in a chair facing the doctor. Images were obtained from both median nerves of the participants. A linear probe was used for imaging the median nerve. The proximal carpal tunnel was defined as the area between the pisiform and scaphoid tubercle; these two anatomical structures were palpated in the palm and easily identified on ultrasound by their hyperechoic surface and strong posterior acoustic shadowing characteristics. The linear probe was placed along the pisiform and scaphoid bones, the probe was kept perpendicular to the median nerve to prevent anisotropic artifact, and the median nerve was visualized in the proximal carpal tunnel.

The wrists of the participants were imaged for the median nerve in the following positions:

Neutral position (fingers in extension) Active maximal flexion position Active maximal ulnar deviation position Active maximal extension position

During position changes, the probe was kept stable and its position was checked before capturing the image. Images were recorded via the ultrasound device.

To test the consistency of ultrasound measurements, imaging of 10 individuals was performed twice with a one-day interval. Measurements were taken and compared. Intraclass correlation coefficient and intra-observer error values were calculated.

Ultrasound Image Analysis

The "ImageJ" program was used to calculate the perimeter and area of the median nerve. The measurement scale in the ultrasound images was proportioned to the number of pixels on the computer screen. Measurements were repeated 3 times and the average of the values was taken.

The circularity formula was defined. A circularity value of 1 indicates that the drawn polygon is a perfect circle; a value less than 1 indicates a deviation from a circle (for example, an oval or irregularly shaped polygon).

To evaluate the deformability of the median nerve, area, perimeter, and circularity deformation ratios were calculated. The deformation ratio was defined as the normalization of the value in different positions with the value in the neutral position. A deformation ratio close to 1 indicates that the ratio in different positions is very similar to the neutral position. The more the deformation ratio deviates from 1, the greater the difference between parameter measurements in neutral and other positions.

Statistical Analysis

The conformity of the variables in the study to normal distribution was evaluated using the Shapiro-Wilk test. Mean±Standard Deviation and Median (Minimum-Maximum) values were used to display the descriptive statistics of the variables.

For comparing Area, Perimeter, Circularity, Area Deformation Ratio, Perimeter Deformation Ratio, and Circularity Deformation Ratio values according to Patient-Control grouping, Independent Samples T-test was used for parameters showing normal distribution, and Mann-Whitney U test was used for parameters not showing normal distribution.

In examining the relationships between Beighton score, age, height, weight, BMI values and Area, Perimeter, Circularity, Area Deformation Ratio, Perimeter Deformation Ratio, Circularity Deformation Ratio values, Pearson correlation analysis was used for parameters conforming to normal distribution, and Spearman non-parametric correlation coefficient was provided for examining relationships between parameters not conforming to normal distribution.

IBM SPSS Statistics 21.0 (IBM Corp. Released 2012. IBM SPSS Statistics for Windows, Version 21.0. Armonk, NY: IBM Corp.) and MS-Excel 2007 programs were used for statistical analyses and calculations. Statistical significance level was accepted as p<0.05.

Inclusion Criteria:

• 15-45 years of age
• Female gender
• Diagnosed with GJH according to the hypermobility spectrum disorders definition
• Patients who agree to participate in the study and provide written consent

Exclusion Criteria:

• Having wrist pain
• Inability to complete full range of motion in the wrist joint
• Patients diagnosed with carpal tunnel syndrome
• Anatomical abnormalities (bifid median nerve, aberrant persistent median artery, Martin-Gruber or other anastomoses)
• History of trauma, operation, fracture, or steroid injection of the hand/wrist
• History of known rheumatological, hereditary, genetic disease, or connective tissue disease other than GJH
• Having neurological disease affecting hand functions (cervical radiculopathy, peripheral nerve lesion, polyneuropathy, cerebrovascular event, etc.)
• Patients with history of regular steroid or non-steroid use, receiving oral glucosamine/hyaluronate supplementation
• Those with systemic diseases (inflammatory joint diseases, diabetes mellitus, acromegaly, hypothyroidism, kidney failure, etc.)
• Having a body mass index (BMI) of 30 or above, or history of morbid obesity
• Being pregnant or in lactation period
• Presence of malignancy

Subjects who met the criteria were selected from those who presented to Istanbul Physical Medicine Rehabilitation Training and Research Hospital.