Hematological Markers in Idiopathic Carpal Tunnel Syndrome

The carpal tunnel, located on the palmar side of the wrist, is bounded medially by the pisiform and hook of hamate, and laterally by the tuberosities of scaphoid and trapezium. The thick connective tissue (flexor retinaculum) covers these four bony prominences, forming a tunnel for the extrinsic flexor tendons of the fingers (flexor digitorum profundus, flexor digitorum superficialis, and flexor pollicis longus), keeping them in place during wrist flexion. The median nerve is the major peripheral nerve of the upper extremity. It originates from the lateral and medial cords of the brachial plexus. It progresses along the arm to the forearm, following a path through the carpal tunnel toward the wrist; here, it branches to provide motor support to the thenar muscle group and sensory innervation to the palmar surface. It innervates the thumb, index finger, middle finger, and half of the ring finger. Carpal Tunnel Syndrome (CTS) occurs when the tunnel narrows or the extrinsic flexor tendons or tendon sheaths swell. It is most commonly seen in the 3rd-5th decades and is three times more common in women than men. The narrowing in the carpal tunnel affects the median nerve, causing sensory disturbance symptoms in the innervated fingers. Symptoms can progress to thenar muscle weakness, leading to weakened grip strength.

Although the pathophysiology of CTS is multifactorial, it can be simplified as compression of the median nerve at the carpal tunnel level. The two most common compression sites are under the flexor retinaculum at the tunnel exit and the hook of hamate. Compression results from increased compartmental pressure in the carpal tunnel and decreased volume. The most common mechanism is hypertrophy of the synovial tissue surrounding the extrinsic flexor tendons of the hand. This hypertrophy may develop due to overuse, wrist trauma, or an underlying inflammatory process such as arthritis. Systemic diseases such as obesity, diabetes mellitus (DM), chronic kidney disease, rheumatoid arthritis, hypothyroidism, congestive heart failure, and pregnancy are also risk factors for CTS.

High body mass index (BMI) is a significant risk factor in developing CTS. A positive correlation between BMI and CTS severity has been reported. CTS is more common in patients with metabolic syndrome, which is characterized by abdominal obesity, atherogenic dyslipidemia, high blood pressure, insulin resistance or glucose intolerance, and is a prothrombotic and proinflammatory endocrinopathy. CTS severity is also higher in these patients.

Environmental workplace factors may promote the development of carpal tunnel syndrome. There is evidence that high levels of repetitive wrist movement increase the risk of carpal tunnel syndrome. There are dramatic changes in fluid pressure in the carpal tunnel according to wrist position; extension increases pressure 10-fold, and wrist flexion increases it 8-fold. Additionally, certain workplace psychosocial factors such as high psychological job demands, high job strain, low level of autonomy over one's work, and absence of interpersonal relationships providing social support are reported to be associated with carpal tunnel syndrome.

Despite various risk factors mentioned above, most CTS cases are still idiopathic cases where the cause cannot be determined. Therefore, comprehensive studies on pathophysiology and etiology continue. In CTS, which can lead to serious disability, a single factor often cannot explain the etiology. Therefore, many risk factors remain unidentified.

In idiopathic CTS, a pathophysiology that triggers each other in the form of ischemia, oxidative stress, low-grade chronic inflammation, and fibrosis, further narrowing the tunnel is emphasized.

In recent years, based on the knowledge that chronic inflammation creates an imbalance in peripheral blood neutrophil, lymphocyte, platelet, and monocyte counts, certain hematological indices have been developed by comparing these blood cells to each other. Commonly used ones are neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), monocyte/lymphocyte ratio (MLR), systemic immune inflammation index (SII) calculated by platelet count X neutrophil count/lymphocyte count formula, and systemic immune response index (SIRI) calculated by neutrophil count X monocyte count/lymphocyte count formula. These indices are reported as simple and useful markers reflecting chronic inflammation in many diseases. In a study conducted with routine hemogram parameters in patients with idiopathic CTS, an increased neutrophil/lymphocyte ratio (NLR) was reported to correlate with CTS severity, and in another study, elevated CRP was reported to correlate with CTS severity, emphasizing systemic inflammation in the etiology of idiopathic CTS.

CTS is the most common cause of acroparesthesia. Beyond classical systemic diseases, growing evidence suggests that metabolic and inflammatory dysregulation may also influence disease severity. In a study comparing patients with moderate and severe CTS, no significant differences were found in terms of age, sex, occupational risk factors, or systemic comorbidities such as diabetes mellitus, hypothyroidism, rheumatoid arthritis, cardiovascular disease, and renal failure. However, higher body mass index (BMI) was significantly more frequent in the severe CTS group. In addition, biomarkers reflecting metabolic and inflammatory status, including the triglyceride-to-HDL (TG/HDL) ratio and composite indices such as the C-reactive protein-albumin-lymphocyte (CALLY) index, may provide further insight into disease severity by capturing underlying low-grade inflammation and metabolic imbalance. These parameters may therefore contribute to explaining inter-individual differences in CTS severity beyond traditional risk factors.