Abstract
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Surgical decompression of carpal tunnel syndrome is usually successful, and failure is rare.
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Diagnosis of persistent or recurrent carpal tunnel syndrome is based on thorough anamnesis and clinical examination, defining underlying comorbidities, nerve conduction studies and distinguish recurrent, persistent or new complaints.
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Management of failed carpal tunnel release may require revision surgery, which includes redo release of the transversal carpal ligament, external neurolysis and flaps.
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A hypothenar fat pad flap or other local, regional or distant flaps may be added to a redo release of the carpal tunnel. Currently, convincing evidence to superiority of additional flap surgery is lacking.
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Postoperative care is evolving toward early motion rather than immobilization, with nerve gliding exercises to prevent adhesions and promote nerve recovery. Virtual reality was recently added to postoperative protocol options.
Introduction
Carpal tunnel syndrome (CTS) is one of the most common compression neuropathies, with a peak incidence between the ages of 40 and 60 years, affecting approximately 1–5% of the adult population. The prevalence of CTS in women is 4:1 compared to men (1). In more than half of cases, the condition is bilateral, presenting with pain or paresthesia in wrist, palm and the first four digits of the hand extending in the forearm and typically worsening at night, what inspired to name it ‘brachialgia paresthetica nocturna’ abbreviated as BPN. As the condition progresses, symptoms may become more pronounced during the day affecting fine motor skills, partially due to thenar atrophy. These complaints often lead patients to consider surgical intervention if nonsurgical treatment options, such as splints, hand therapy (HT) and corticosteroid injections, failed to provide relief (2).
Both endoscopic and open releases of the transverse carpal ligament (TCL) are widely used surgical techniques to decompress the median nerve (3). While most patients experience significant symptom relief after surgery, complications and failures occur in 3–25% of cases. It is crucial to distinguish between recurrent symptoms – those reappearing after a symptom-free period of more than 6 months – and persistent symptoms, which either remain unchanged or newly develop after the initial primary release (4). Postoperative numbness and paresthesia can be normal after CTS release surgery, but recover partially or completely. However, due to scar tissue formation, incomplete release or perioperative nerve injury lasting and new symptoms can be challenging to determine the appropriate treatment strategy.
To address recurrent CTS after surgical decompression, various surgical options have been described ranging from simple open revision up to interposition techniques to isolate the nerve and prevent the split transverse ligament endings to rejoin. These interposing tissues may involve local, regional or distant fat flaps and the use of free fat grafting and adhesion barrier gels. However, there is no clear consensus on the most optimal surgical approach.
It is believed that an early, active postoperative rehabilitation plays a vital role in preventing perineural adhesion both in primary and revision carpal tunnel release. Recently, immersive virtual reality (VR), guided by a hand therapist, was incorporated as a promising tool to enhance patient engagement and to facilitate faster and safe functional recovery by stimulating hand–brain interactions (5).
Failure of carpal tunnel release
Symptoms: recurrent, persistent or new?
Identifying the origin of symptoms in patients with carpal tunnel median nerve compression symptoms after surgery is crucial. It is important to differentiate patients with recurrent symptoms – those who experienced a symptom-free period after the initial surgery- and patients experiencing persistent or new symptoms. Recurrent symptoms are defined as those that fully disappeared after primary surgery but reappeared after at least six months, presenting again as pain, paresthesia and increasing numbness (6). Persistent symptoms such as residual pain, paresthesia and lasting numbness after the initial release may indicate an incomplete decompression of the median nerve. The persistence of symptoms needs to be differentiated from new symptoms arising immediately after surgery, since they may suggest reactive neuritis after decompression or even potential iatrogenic damage to the median nerve by rough manipulation or sharp dissection. These two conditions require distinct treatment approaches. For persistent symptoms due to incomplete surgical decompression, revision surgery may be considered to more extensively release the TCL. This approach may provide immediate relief and allow rapid rehabilitation. For nerve damage-related symptoms, commonly including allodynia, hyperalgesia and hypoesthesia to touch and pinprick, persistent neuropathic pain is more likely, and surgical exploration is still recommended, although it may not improve such complaints (7).
Differential diagnosis of symptoms
Thorough anamnesis and clinical examination focusing on the onset, progression and nature of the symptoms is emphasized in detail by Hagert et al. who describes the triad-of-Hagert, a structured approach involving manual muscle testing, sensory collapse testing and pain evaluation to enhance diagnostic precision (8). Scoring tools and provocative tests such as Phalen’s and Tinel’s signs, along with an assessment for thenar muscle atrophy are commonly used (9). In addition, evaluating the motor function of the flexor pollicis longus, flexor digitorum profundus (particularly of the index and middle fingers) and the pronator quadratus is essential to rule out anterior interosseous nerve (AIN) entrapment, a condition affecting the proximal median nerve (10). Nerve conduction studies, such as electromyography (EMG), are used to confirm the diagnosis, determine severity and exclude other proximal pathologies such as AIN or cervical radiculopathy (11). However, it is important to note that 5–25% of patients with clinically suspected CTS may have normal EMG results, necessitating more advanced diagnostic techniques (12). Magnetic resonance imaging (MRI) and ultrasonography (US) can be valuable tools for the differential diagnosis of CTS (13).
Reasons for recurrence or persistence
The recurrence of median nerve entrapment at the carpal tunnel is multifactorial. Numerous underlying pathologies have been well documented in the literature and should be considered when establishing a differential diagnosis for recurrent CTS. Environmental, occupational and anthropometric factors have been shown to contribute to disease risk. However, in most cases, no specific cause or underlying condition can be identified. In this discussion, we highlight some rather unusual cases of distal median nerve entrapment at the carpal tunnel covering genetic, systemic and space-occupying causes (2).
CTS and childhood
While CTS is common in adults, it is extremely rare in children. Both genetic and non-genetic causes have been described, as reviewed by Van Meir et al. (14, 15). Non-genetic causes include idiopathic CTS, sports-related CTS, fibrolipomatous hamartoma, intraneural perineuroma, hemangioma of the median nerve, macrodactyly, metabolic diseases (such as pseudohypoparathoidism), musculotendinous malformation, trigger finger, Klippel–Trénaunay syndrome, Poland syndrome, scleroderma and trauma. Genetic conditions, however, are more frequently associated with pediatric CTS, with lysosomal storage diseases – such as mucopolysaccaridosis and mucolipidosis – being the most common etiologies. Other, rarer genetic causes include primary familial CTS, hereditary neuropathy pressure palsy, Albright hereditary osteodystrophy and acromicric dysplasia. Moreover, new genetic variants continue to be identified. Peeters et al. recently reported a novel fibrillin-2-related disorder by identifying a new FBN2 variant (p.Phe 1670Cys) in a unique family, which was linked to early-onset CTS (16). This newly described fibrillinopathy of fibrillin-2 (FBN2) falls within a spectrum of disorders exhibiting opposing phenotypes. Heterozygous pathogenic variants in FBN1 and FBN2 can lead to conditions associated either with tall stature and arachnodactyly (such as Marfan syndrome (FBN1) and congenital contractural arachnodactyly (FBN2)) or short stature and brachydactyly (such as stiff skin syndrome, Weill–Marchesani syndrome, geleophysic dysplasia and acromicric dysplasia in FBN1 versus FBN2-related acromelic dysplasia) (17). The family described by Peeters et al. appears to expand the spectrum of fibrillin-2-opathies, presenting with an acromelic dysplasia-like phenotype. Clinical features included short Achilles tendon, leading to toe-walking in childhood, brachydactyly type brachymesophalangy type A2 or A3 (Temtamy) and biphalangeal toes (Figs 1 and 2). Other distinctive features included facial dysmorphism, short nose, broad nasal bridge and almond-shaped eyes along with short stature, although mental development remained completely normal. Early surgical intervention is important in these cases and should be performed as soon as the genetic disorder is confirmed to improve recovery of the entrapped median nerve. In some cases, surgery has been performed on infants as young as 3-months-old due to severe clinical symptoms such as thenar muscle atrophy, pain and numbness. In this family, all surgical interventions – whether primary or revision surgeries – were performed using a hypothenar fat pad (HFP) flap (Fig. 3). A striking clinical sign of pediatric CTS is a child using a touchscreen device (such as smartphone or tablet) exclusively with the fourth and fifth digit, as they lose sensation in the radial digits. This should be considered a red flag in the diagnostic process for CTS in young patients. In addition, flexor tendon tenosynovitis or trigger fingers often co-occur and should not be overlooked. Due to the very early onset of CTS in these patients, there is a high risk of recurrence in adulthood, emphasizing the need for long-term follow-up and management.
X-ray with brachymesophalangy Temtamy type A2 (digit II and V).
Citation: EFORT Open Reviews 10, 6; 10.1530/EOR-2025-0058
X-ray with brachymesophalangy Temtamy type A3 (digit V only).
Citation: EFORT Open Reviews 10, 6; 10.1530/EOR-2025-0058
Compression site of median nerve in revision surgery of a congenital FBN2 gene CTS.
Citation: EFORT Open Reviews 10, 6; 10.1530/EOR-2025-0058
CTS and ATTR amyloidosis
A variety of systemic conditions, including diabetes mellitus, hypothyroidism, obesity and metabolic disorders, are associated with carpal tunnel entrapment disease. Temporary hormonal imbalances and swelling can also contribute to CTS during pregnancy. We particularly highlight the association between transthyretin cardiac amyloidosis (ATTR-CA) as a cardioorthopedic disease and its potential role in the failure of primary carpal tunnel release and recurrent symptoms (18). ATTR-CA is caused by the extracellular myocardial deposition of misfolded transthyretin, a plasmatic protein produced mainly by the liver that carries thyroid hormones and retinol in the blood. When this protein misfolds, it results in amyloid fibers that precipitate and deposit in many tissues, leading to structural alterations, dysfunction and heart failure with early death. Different types of amyloidosis exist, including ATTR, AL (light chain) and AA (amyloid A), with ATTR being the most relevant in this context. ATTR amyloidosis can be further classified into two types: a rare inherited genetic variant (ATTRv), prevalent in specific geographic regions, and the more common wild-type (ATTRwt). Early diagnosis of this disease is crucial to prevent progression and death. Bilateral carpal tunnel symptoms in men over 50 or women over 60, along with primary or early recurrent CTS and other musculoskeletal manifestations, such as trigger finger, spinal canal stenosis, biceps tendon rupture, joint articulation accumulation (shoulder/hip/knee) and even hearing dysfunction, are recognized as red flags, appearing 5 to 15 years before the cardiovascular symptoms, particularly in cases of CTS and trigger finger (19).
A biopsy of tenosynovial tissue taken from around the flexor tendons in the carpal tunnel or at the ligamentum transversum carpi is helpful to find misfolded protein deposition suggestive of ATTR-CA. Congo red staining is used to detect amyloid deposition, with the possibility of having subtype analysis and protein identification. Biopsies are classified according to Westermark score (20). While endoscopic carpal tunnel release may yield a lower detection rate of amyloid deposits than during open carpal tunnel release, experienced practitioners can achieve reliable biopsy results with either technique (21). The absence of cardiac symptoms in many patients with positive biopsies underscores the primordial role of these biopsies in early detection (22). Bone scintigraphy is recommended for assessing cardiac tracer uptake, with the Perugini score visually quantifying amyloid deposits in the myocardium and ribs (23). Fortunately, medical treatment for ATTR-CA has become available in recent years, offering hope for patients with progressive heart failure. The optimal timing for initiating therapy remains uncertain, but early follow-up in a heart failure management program is crucial and could be lifesaving over the next 10 to 15 years. The production of transthyretin in the liver can be blocked by agents such as patisiran, notersen, vutrisiran or eplotersen, or stabilized with tafamidis or diflunisal. Future treatment strategies, including CRISPR-Cas9 gene-editing therapy, hold promise for directly targeting the genetic cause of the disease, potentially stopping progression and improving clinical outcomes. Ongoing studies will determine the efficacy of gene-editing tools as alternative treatments alongside other gene-silencing medications and stabilizers of the TTR tetramer (24). Combining TTR production reduction (patisiran) with TTR stabilization (tafamidis) may have synergistic effects and further improve patient outcomes (25).
In conclusion, performing a biopsy, particularly during carpal tunnel revision surgery, should be considered to assess for amyloidosis. Existing clinical flowcharts assist physicians in deciding whether to perform an intraoperative biopsy (26). However, discrepancies in reimbursement policies across countries necessitate more specific decision-making models. The cost of biopsying every patient undergoing carpal tunnel surgery may be prohibitive, given the financial constraints of different health systems. More refined models incorporating cardiac parameters (e.g., troponine and NT-proBNP), echocardiographic and electromyographic characteristics, light chain dosage and paraprotein immunofixation can enhance the selection of patients for biopsy. The combination of these parameters, alongside clinical signs and musculoskeletal manifestations, is essential in optimizing diagnostic accuracy and guiding clinical decisions.
CTS and tumors
Space-occupying lesions within the carpal tunnel can lead to CTS and may require surgical excision. Tumors of the median nerve, including intraneural lipoma, schwannoma, hemangioendothelioma and fibrolipomatous hamartoma, are rare and even more exceptionally found bilaterally (27, 28, 29) (Fig. 4). Ultrasonography and MRI are essential to accurately differentiate these lesions to plan an appropriate surgery, such as external neurolysis or epineurolysis, with or without the wrap-around technique. Preoperative routine ultrasonography during outpatient clinics is highly recommended. This imaging modality can be very valuable in identifying external compression causes within the carpal tunnel or more proximally at the radiocarpal crease. We reported a case in which an unexpected source of median nerve compression was identified: a screw from a previous plate-and-screw osteosynthesis for a distal radial fracture, which was in direct contact with the nerve and causing symptoms (30).
T1 and T2 MRI images of a fibrolipomatous hamartoma.
Citation: EFORT Open Reviews 10, 6; 10.1530/EOR-2025-0058
Treatment of failed carpal tunnel release
Rationale for revision surgery
If recurrent compression of the median nerve is obvious and symptomatic and if maximal conservative treatment – such as HT or corticosteroid injections as a trial treatment – has failed, revision surgery may be preferable. In case of reintervention for CTS following a previous endoscopic or open release, an open surgical technique seems logical. However, the decision to cover the median nerve with a flap remains unclear in literature.
Surgical technique of revision surgery
A revision surgical procedure starts with reopening the carpal tunnel and exploring the median nerve while carefully managing fibrotic tissue surrounding it and the release of adhesions with the TCL. If necessary, the incision may need to be extended proximally in a Bruner fashion across the wrist crease to release the antebrachial fascia or distally beyond Kaplan’s line, approaching the deep and superficial vascular arc between the radial and ulnar arteries to allow identifying normal median nerve tissue (31). This procedure is relatively straightforward. However, in cases where new symptoms arise due to an overly aggressive primary release or if a median nerve tumor is identified as the cause of surgical failure, a conservative and minimally invasive treatment approach is often recommended, given the limited success rates of revision surgery. Peripheral nerve stimulation is emerging as a potential alternative in select cases. This technique involves the electrical stimulation of a nerve trunk or ganglion via subcutaneous electrodes placed near the target nerve. The therapeutic mechanisms include activating non-nociceptive fibers to suppress nociceptive conduction, promoting the release of endogenous opioids such as endorphins and exerting anti-inflammatory effects offering promising advancements in chronic pain management (32).
Next to the nerve (re-) decompression, various additional flap options are available, including local flaps such as the HFP flap, regional flaps such as the radial forearm adipofascial flap, and distant flaps such as the pedicled groin flap (2). These techniques aim to prevent median nerve adherence and scarring by creating a protective barrier between the nerve and the TCL.
The HFP flap, initially popularized by Cramer and Strickland, is one of the most commonly used techniques to surgically address recurrent CTS (33). The fat pad is harvested from the hypothenar eminence along the ulnar border of the carpal tunnel incision. Its vascular pedicles, originating from the ulnar artery within Guyon’s canal, are mobilized and positioned over the median nerve, securing the flap to the radial border of the TCL, after carefully visualizing and securing the motor branch of the median nerve (Figs 5 and 6).
Revision surgery of recurrent CTS opening TCL and harvesting HFP flap.
Citation: EFORT Open Reviews 10, 6; 10.1530/EOR-2025-0058
Interposition of HFP flap under the radial border of the TCL in revision surgery CTS.
Citation: EFORT Open Reviews 10, 6; 10.1530/EOR-2025-0058
We conducted a systematic review assessing the added value of a hypothenar fat flap procedure compared to a simple open carpal tunnel release in revision surgery cases. After screening 764 articles using the PRISMA method, only nine articles met the criteria for data extraction. However, none of these fully adhered to the study criteria due to lack of comparative studies. A major issue was the inclusion of mixed patient groups, where different types of complaints were analyzed together. Defining recurrence as the key indication for revision surgery remains of paramount importance.
Besides flaps, other methods such as fat grafting and anti-adhesion gel barrier placement need further scientific research (2).
Outcome of revision surgery
Revision surgery for CTS generally results in improvement, but outcomes are often less favorable compared to primary carpal tunnel release. Informed consent should be obtained and postoperative expectations well described. Predictors of better outcomes include absence of diabetes and tobacco use, less preoperative pain and use of preoperative steroid injections (34).
Perioperative setting plays a crucial role in patient outcomes and experiences. Distraction techniques such as noise-canceling headphones or VR, thorough patient education via informed consent and digital patient journey apps, and intraoperative participation through locoregional anesthesia or WALANT technique (Wide-Awake Local Anesthesia No Tourniquet) technique contribute to improved patient tolerance. In patients with a history of complex regional pain syndrome (CRPS), perioperative bisphosphonate administration combined with immediate postoperative physiotherapy may help optimize recovery (35, 36).
Postoperative rehabilitation
Revision surgery for failed carpal tunnel release is associated with a high risk of complications, particularly due to the potential for persistent postoperative neuropathic pain. To minimize this risk, diagnosis needs to be clarified, meticulous surgical technique is crucial and postoperative immobilization should be minimized. Nevertheless, a delay in achieving full functional recovery is possible. HT can play a key role in restoring a functional, pain-free hand with the choice of techniques depending on the specific issues present. These may include restricted mobility, reduced strength, problematic scar formation, pain and sensory disturbances leading to functional limitations. A range of therapeutic techniques – often combined – may be employed, such as manual mobilizations, neurodynamic mobilizations, silicone scar dressings, ultrasound therapy, electrotherapy and exercise therapy. Given the limited availability of strong scientific evidence, treatment should be guided by the expertise of the hand therapist and tailored to the patient’s preferences and clinical context (37). In recent years, technological advancements have introduced new opportunities for rehabilitation. Telerehabilitation via tablet-based platforms has shown greater effectiveness than traditional home exercise programs, and when combined with standard physiotherapy, it may accelerate functional recovery and return to work, as demonstrated by Blanquero et al. (38, 39). Moreover, VR is emerging as a promising tool to facilitate early active engagement (40). Using hand tracking or controllers, patients can perform functional tasks and exercises, and future developments may enable neurodynamic mobilizations through VR applications (5) (Fig. 7). Beyond treatment, hand therapists can provide surgeons with valuable assessment outcomes that may support follow-up care (41).
Neurodynamic mobilizations with early active motion using VR.
Citation: EFORT Open Reviews 10, 6; 10.1530/EOR-2025-0058
Conclusion
An effective approach to failed carpal tunnel release starts with a thorough medical history, clinical examination, nerve conduction studies such as EMG and visualization techniques, such as ultrasonography and MRI, to precisely determine the cause of the persistent or recurrent symptoms and the indication for revision surgery. It is essential to identify whether symptoms are recurrent, persistent or new. Recognizing associated pathologies and less common causes of carpal tunnel entrapment is also critical to guide decision-making. The importance of a tailored, individual treatment plan cannot be sufficiently emphasized. In revision surgery, a simple release, the use of locoregional flaps or barrier interposition may be considered. While the outcome of revision surgery is inherently uncertain, a standardized approach, consistent perioperative management and preparing the patient and their support system – alongside an early hand rehabilitation protocol – may significantly improve the chances of achieving an acceptable long-term result in these complex cases.
ICMJE Statement of Interest
I declare there is no conflict of interest that could be perceived as prejudicing the impartiality of the work reported.
Funding Statement
This work did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.
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