Double Crush Syndrome: A Review of the Literature

Abstract

Double crush syndrome (DCS) is a condition characterized by multiple compression sites along a single peripheral nerve. The purpose of this review is to provide a focused review of the incidence, the most likely pathology, the best diagnostic tools and parameters, and treatment recommendations for DCS that have evolved in recent years. Currently reported incidence of DCS ranges broadly from 6.7% to 73%, which may be due to lack of established anatomic electrodiagnostic criteria to define DCS. Treatment outcomes were diverse, emphasizing the lack of consensus on optimal management strategies. The review underscores the persistent ambiguity surrounding DCS, with inconclusive evidence on its pathophysiology and diagnostic criteria. This study highlights the need for a multidisciplinary approach, emphasizing thorough diagnostic workup to set properly patient expectations for treatment if DCS is suspected. In addition, conflicting outcomes from treatment modalities highlight the complexity of managing this syndrome. The lack of consensus on various aspects of DCS necessitates further research to guide more effective diagnostic and therapeutic approaches.

Introduction

Double crush syndrome (DCS) is a condition characterized by the presence of multiple insults along a single peripheral nerve or neural pathway (i.e. peripheral nerve compression and cervical spinal cord compression), where the cumulative effect of these insults results in symptoms that are more severe and debilitating than what would be expected from a single nerve insult. ¹ However, there is still no consensus definition. The most challenging aspect of DCS is the difficulty in confirming the diagnosis. Health care personnel diagnose peripheral compression neuropathy, cervical root or spinal cord compression following a thorough history and physical examination. ¹ Further testing may include electrodiagnostic testing, magnetic resonance imaging (MRI), and ultrasound. ¹ We do not currently have a single diagnostic test to confirm or rule out DCS.

This syndrome was first described in the orthopedic literature in 1973 by Upton and McComas, ² who identified a high occurrence of cervical radiculopathy in patients concurrently suffering from carpal tunnel syndrome (CTS) and cubital tunnel syndrome (CubTS). Case studies have reported nonanatomic structures causing compression at both the proximal and distal nerve or a compressive lesion in conjunction with peripheral neuropathy, causing synergistic effects on patient symptoms.^3,4 There are conflicting opinions on the pathophysiology of this presentation. The overall incidence and epidemiology of the condition remain uncertain. An extensive diagnostic workup is required to reveal the lesions with various underlying causes, which must be identified and treated to achieve adequate symptomatic relief.

The purpose of this review is to provide a focused review of the incidence, the most likely pathology, the best diagnostic tools and parameters, and treatment recommendations for DCS that have evolved in recent years.

Proposed Pathophysiology

The discrete pathophysiological mechanism(s) of DCS have remained ambiguous. The challenge of confirming the mechanism(s) of DCS may be due to no objective measure to verify pathophysiology at 2 levels of a peripheral nerve. Upton and McComas ² introduced the concept that impaired axoplasmic flow could predispose one site to nerve entrapment, compression, or injury when another site is already affected (Figure 1). Injury to an axon disrupts the transport of essential nutrients, resulting in functional change and increased susceptibility to further injury. ²

Figure 1.

Pathophysiological theories of DCS: (a) This schematic depicts the axonal transport theory of DCS. Proximal compression or injury causes reduced blood and endoneurial flow, resulting in increased susceptibility for distal nerve injury. Subsequent distal injury causes further reduction in blood and endoneurial flow, worsening symptoms and functional impairment. (b) This schematic depicts the ion channel regulation theory of DCS, which theorizes that a nerve injury causes upregulation of Na+ channels and a downregulation of K+ channels, resulting in a higher resting membrane potential and lowered firing voltage. This inclination to depolarize has been associated with neuropathic pain.

Source. Image produced on BioRender.com.

Note. DCS = double crush syndrome.

Although electrodiagnostic studies have failed to demonstrate this proposed pathophysiology in humans, several canine models are consistent with the historical definition.^{5 -8} In a study of 46 canines, nerve compression resulted in decreased blood flow and axoplasmic flow with increased endoneurial pressure. ⁷ More proximal lesions had a larger impact on nerve dysfunction. ⁴ Dellon and Mackinnon ⁷ also described the synergistic nature of DCS, finding in their canine model that 2 lesions on a nerve at the same time produced a significantly greater electrophysiological impairment than the sum of 2 separate lesions on a nerve at different times. ⁸

Pathophysiological mechanisms involving the cervical spine have also been proposed and explored. In 1984, Good et al ⁹ proposed that “numb, clumsy hands” and stereo-anesthesia in the setting of cervical myelopathy may be due to high cervical spondylosis between the foramen magnum and C5 vertebra. Stereo-anesthesia is a condition that impairs the ability to recognize the form and nature of objects by touch. ¹⁰ More recent bilateral quantitative assessments of MRI with supporting clinical history and nerve conduction velocity (NCV) tests have found narrowed cervical foramina and affected nerve roots on the same side as CTS symptoms in patients with DCS.^11,12 Despite these pathophysiological studies and explanations, experts and orthopedic surgeons remain unconvinced. A Delphi study surveying 16 field experts revealed other proposed mechanisms that are yet to be fully investigated, including: (1) ion channel up or downregulation; (2) immune inflammation of the dorsal root ganglia; and (3) neuroma in continuity. ¹³

In addition to the pathophysiologic uncertainty of DCS, the clinical significance of its proposed mechanism(s) also remains unclear. Richardson et al ¹⁴ analyzed the prevalence of median mononeuropathy in a subpopulation of patients with cervical radiculopathy. The authors found that those with cervical radiculopathy had a higher prevalence of median mononeuropathy than the standard low-risk population, reinforcing the association present in DCS. ¹⁴ However, this study’s electrophysiological findings seem to refute their proposed mechanism, and the authors suggest that other inciting factors, such as occupation, sex, or obesity, may promote DCS. ¹⁴ Similarly, Chaudhry and Clawson ¹⁵ contradicted the DCS predisposition, finding that a systemic motor neuron disease, amyotrophic lateral sclerosis (ALS), for example, did not increase susceptibility of distal nerve lesions. However, the authors did find that nerves with multiple lesions (ALS and entrapment) had lower motor amplitudes and unchanged sensory amplitudes on electrophysiology, substantiating the synergistic aspect of the DCS claim. ¹⁵ While there are many proposed mechanisms supporting the DCS hypothesis, there is still no consensus on the pathophysiology of this presentation.

Many individuals with potential DCS may still experience symptoms from 2 completely unrelated musculoskeletal pathologies such as cervical disk disease and peripheral nerve compression. The cervical disk disease can be in the setting of a straightforward radiculopathy or a more complex myelopathy. Myelopathy is particularly problematic as the physical examination presentation can be variable and is not as concise as the physical examination in radiculopathy. For example, a patient with central disk protrusion or posterior cervical spine osteophytes who has myelopathy from anterior pressure on the spinal cord can often present with hand numbness and weakness, mimicking CTS. However, myelopathy will present with hyperreflexia, whereas radiculopathy and CubTS will present with hyporeflexia, highlighting the importance of a thorough physical examination. ¹⁶ This scenario of separately identified radiographic cervical disk disease with nerve conduction study-confirmed CTS or CubTS is a common presentation for DCS.

Incidence and Epidemiology

Double crush syndrome is often diagnosed after patients undergo carpal or cubital tunnel release (or even cervical spine surgery) and feel dissatisfied with the results. ¹ Thus, researchers have sought to establish true disease incidence to help distinguish isolated neuropathies from DCS before surgical management. The currently reported incidence of DCS ranges broadly from 6.7% to 73%, which may be due to lack of established anatomic electrodiagnostic criteria to define DCS.^1,3,17 Mills et al ¹⁷ conducted a large retrospective database study that assessed for potential DCS and found that of the more than 900 000 patients previously diagnosed with cervical radiculopathy, 9.98% and 3.15% had additional CTS and CubTS, respectively. These findings underscore a high disease prevalence with potential implications for surgical intervention. However, Morgan and Wilbourn came to a different conclusion in their retrospective study of DCS, stating that cervical radiculopathy rarely did serve as the proximal lesion in the diagnosis of DCS. They argue that there is inconsistent reporting of the proximal lesion due to lack of delineation between demyelinating versus axonal injury, which may confound previous articles. ¹⁸ Axonal loss refers to the death or damage of nerve fibers, while demyelination describes the damage or loss of the myelin sheath, leading to impaired nerve signal transmission. ¹⁹ However, because both injuries cause nerve dysfunction, we argue that delineation is not relevant, and both would contribute to a proximal lesion in DCS. Another retrospective analysis of 765 patients with suspected cervical radiculopathy and CTS reported that the average age of patients was 50 to 55 years, consistent with other reports, with a higher prevalence of CTS in women and similar percentages of cervical radiculopathy between both sexes.^3,20,21 However, these findings conflict with studies reporting a higher incidence of DCS in men and older patients.^20,22,23

Regarding symptomology and clinical presentation, Osterman found that subjective grip strength disability was significantly more common among DCS patients versus CTS alone. ²⁴ In a recent retrospective analysis of 32 surgical patients with a clinical diagnosis of cervical radiculopathy and CTS, Ochoa-Cacique et al ³ discovered that DCS is most commonly identified in patients with unresolved postoperative symptoms, with paresthesia in the C6 dermatomal distribution being the most bothersome complaint (65.6%), further corroborating previous reports. ²⁴ Osterman ²⁴ also highlighted systemic hypertension as a potential associated independent risk factor, adding to Baba et al’s ²³ findings, which identified a higher incidence of compressive neuropathies among diabetic patients, with 16% of patients having both CTS and CubTS.

In a case-controlled study of 20 female patients with DCS and 21 controls, Kaya et al ²⁵ found that patients with DCS report moderate to severe pain and disability, with numbness as the most bothersome clinical symptoms. These patients also had significantly increased thoracic and lumbar spine curvature and decreased spine mobility. ²⁵ Furthermore, Lo et al ²⁰ uncovered a higher incidence of wrist and hand weakness in patients with sole cases of cervical radiculopathy, suggesting that cervical root lesions cause more profound motor deficits in the upper extremities than CTS alone.

Clinical Presentation and Diagnosis

While a proposed theory of DCS is nerve symptomatology from 2 distinct nerve lesions, there is no clear consensus on what qualifies the diagnosis (Figure 2). Diagnosis is further complicated by the many causes that can cause nerve damage, with these causes occurring at either the proximal or distal lesion. Creating a set of diagnostic criteria that encompasses all possible presentations poses a significant challenge. We do not currently have a singular test to simultaneously determine central and peripheral nerve compression. While nerve conduction studies may potentially help to find multiple lesions on the same nerve, there may still be overlap in determining lesion type which makes determining whether there are 2 distinct crush injuries challenging. ²⁶

Figure 2.

This schematic diagram depicts the clinical impact of double crush syndrome. Those with proximal and distal lesions along the same nerve have a synergistic effect, resulting in worsened symptoms and further functional impairment (Image produced on BioRender.com).

Double crush syndrome patients commonly present with peripheral sensorimotor neuropathy. This neuropathy may include sensory loss, burning or tingling sensation, decreased limb dexterity, limb weakness, or lack of coordination. ¹ In addition to classic peripheral neuropathy, clinicians must also consider the possibility of an additional lesion proximal to the symptoms in the peripheral or central nervous syndrome (CNS). Additional CNS symptoms may include radiating nerve pain, paresthesia, loss of sensation, hand and upper extremity weakness, hyperreflexia, balance impairment, Lhermitte’s sign, and loss of fine motor control. ¹ Lesions may arise from systemic diseases, malignancies, nonanatomic structural compression, or other causes.^{26 -28} Potential risk factors as seen across literature are summarized in Table 1. Misdiagnosis of DCS is common, given the extensive number of risk factors, and would therefore benefit from coordination between multiple subspecialties. For example, when an individual presents with symptoms of CTS for which a hand surgeon can treat, a subsequent radiculopathy would need to be treated by a spine surgeon. Similarly, for an individual with a compressive nerve lesion and a medical neuropathy, the lesion should be decompressed by an orthopedic surgeon, but the patient must also be followed by a medical doctor, such as a neurologist or others depending on the cause.

Table 1.

Potential Risk Factors for Double Crush Syndrome Separated Into Various Etiological Categories.

Etiological category	Risk factors
Neuropathy and nerve compression 1	- Carpal tunnel syndrome - Cubital tunnel syndrome - Cervical radiculopathy - Thoracic outlet syndrome - Lumbar radiculopathy - Sciatic nerve entrapment
Repetitive motion and overuse 1	- Prolonged computer use (e.g., typing and gaming) - Repetitive hand/wrist movements (factory work, musicians, and assembly line work) - Heavy lifting or overhead work (construction, electricians, and athletes) - Sports overuse (baseball pitchers, weightlifters, and rock climbers) - Long-term wheelchair use
Metabolic disorders 4	- Diabetes mellitus - Hypothyroidism - Obesity - Dyslipidemia - Long-term kidney disease - Metabolic syndrome
Inflammatory and autoimmune conditions 4	- Rheumatoid arthritis - Systemic lupus erythematosus - Sjögren’s syndrome - Long-term inflammatory demyelinating polyneuropathy - Multiple sclerosis - Sarcoidosis
Trauma and structural abnormalities 1	- Previous fractures or dislocations (e.g., wrist, elbow, shoulder, and spine) - Cervical or lumbar disk herniation - Congenital anomalies (e.g., cervical rib and bifid median nerve) - Scar tissue from surgery or injury - Spinal stenosis - Scoliosis
Lifestyle and occupational factors 1	- Poor posture (e.g., forward head posture and excessive neck flexion) - Sedentary lifestyle - Long-term stress - Vibration exposure (e.g., power tools, jackhammers, and driving heavy machinery) - Smoking
Vascular and circulatory factors 29	- Peripheral vascular disease - Raynaud’s phenomenon - Long-term ischemia - Atherosclerosis
Genetic and age-related factors 22	- Older age (degenerative changes) - Family history of neuropathy - Hereditary neuropathies (e.g., Charcot-Marie-Tooth disease)
Nutritional deficiencies 4	- Vitamin B12 deficiency - Folate deficiency - Thiamine deficiency - Vitamin D deficiency
Connective tissue disorders 4	- Ehlers-Danlos syndrome - Marfan syndrome - Hypermobility spectrum disorders - Dupuytren’s contracture
Medications and toxic exposures 4	- Chemotherapy drugs (platinum-based drugs) - Alcoholism - Heavy metal toxicity (lead, arsenic, and mercury) - Statins
Long-term pain and central sensitization 1	- Fibromyalgia - Long-term regional pain syndrome

Physicians have a variety of physical examination maneuvers and imaging modalities available to diagnose CTS and CubTS; however, these may lead to some confusion with less straightforward results in patients with DCS. The Tinel’s and Phalen’s tests are routinely used in diagnosing CTS, with reported sensitivities of 90.2% and 85.4% and specificities of 65% to 91% and 17% to 88%, respectively. ²⁰ However, these tests have no ability to demonstrate a potential proximal lesion. Lo et al ²⁰ also found that typical CTS physical examination findings were more common in patients with CTS alone, whereas patients with DCS less commonly presented with Tinel’s and Phalen’s signs. Meanwhile, cervical radiculopathy or myelopathies alone may also present with signs of decreased hand dexterity and difficulty completing fine motor tasks, further complicating the evaluating physician’s ability to distinguish between isolated compressive lesions and DCS.^30,31

A study by Donaldson et al ³² displayed that neck positioning and musculature has an effect on the distal limb symptoms seen in CTS. In a clinical trial of 18 patients, all showed asymmetrical neck musculature and significant changes in electromyography (EMG) measurements of the forearm flexors and extensors during head rotation, flexion, and extension. This finding provides an opportunity to identify cervical lesions with neck muscular dysfunction in patients presenting with CTS. It was also found that neck muscle retraining both relieved symptoms and normalized the EMG measurements, displaying restored muscle activation. ³² Conversely, Davidge et al, ³³ who studied a presentation of DCS with both lesions occurring in the distal upper extremity, highlighted the utility of the hierarchical scratch collapse test to evaluate multifocal ulnar nerve compression. The premise of this test is to anesthetize the area of greatest nerve damage to uncover additional lesions that may be masked by the symptoms of a larger lesion. The study found that using topical ethyl chloride at the point of maximal ulnar nerve compression provided the ability to test subsequent compression points along the ulnar nerve and uncover additional lesions. ³³ While this test is helpful in CubTS, it is uncertain if similar tests could be used for other locations of DCS.

Regardless of the physical examination, the currently accepted gold standard for diagnosing DCS is EMG for peripheral neuropathy and MRI scan for cervical disk disease. ²⁰ Electromyography cannot simultaneously detect a proximal nerve lesion when a patient is being evaluated for a distal lesion. Lee et al ³⁴ describes a case of ulnar nerve injury in which electrodiagnosis showed clear compression around the elbow, but further ultrasound studies revealed a second compression site in the wrist. Thorough preoperative examination of the entire ulnar nerve ensured resolution of symptoms after dual ulnar decompression in a single procedure. Lee et al ³⁴ therefore argues for the utility of ultrasound for examination of the affected nerve.

In addition to the peripheral diagnostic tests, further examination of potential proximal lesions must be examined to diagnose DCS. For patients presenting with CTS, Flak et al ¹² discusses the utility of cervical radiographs to illustrate cervical discopathy that may be causing cervical radiculopathy. Flak et al ¹² in agreement with Pierre Jerome and Bekkelund, ¹¹ also discusses the utility of MRI in diagnosing a central nerve lesion in DCS. As the gold standard for cervical disk disease imaging, MRI exposes potential radiculopathy based on signs of narrowing of the intravertebral foramina, present in 81.25% of DCS patients, and significant narrowing of the vertebral canal, present in 37.5% of patients with DCS. ¹² However, these signs do not guarantee the presence of radiculopathy. Another retrospective study of 19 patients with weakness and atrophy of intrinsic hand muscles found that patients had compression of C7 (n = 9), C6 (n = 12), C5 (n = 8), and C4 (n = 2). ³⁵ Magnetic resonance imaging subsequently confirmed cord compression in all but 3 of these patients. ³⁵ Despite this demonstrated utility, there is yet to be a clear guideline on when a patient has high-enough suspicion to undergo MRI for confirmatory diagnosis of DCS. Table 2 Summarizes currently used diagnostic studies and their efficacy.

Table 2.

Summary of Diagnostic Studies Used in Double Crush Syndrome Diagnosis and Their Reported Ranges of Sensitivity and Specificity.

Diagnostic tool	Sensitivity (%)	Specificity (%)
Nerve conduction studies 36	89	80
Electromyography for peripheral nerve disease 37	60-80	70-90
MRI for cervical disk disease 38	86-97	72-86
MRI for peripheral nerve lesions 37	85-95	75-90
Ultrasonography 37	76	85
Tinel’s sign 20	90.2	65-91
Phalen’s test 20	85.4	17-88
Scratch collapse test 39	37	94
Katz hand diagram 40	64	73
Cervical radiographs for cervical discopathy 38	70-80	60-85
Carpal tunnel syndrome - 6 risk score 41	84	91

Note. MRI = magnetic resonance imaging.

Overall, the diagnosis of DCS uses both clinical and radiological findings. There is not an agreed upon diagnostic algorithm but instead requires diligent history taking, clinical reasoning, and investigation to uncover DCS. Correctly diagnosing DCS is essential for setting accurate expectations prior to intervention. For example, if a clinician suspects DCS, communicating with the patient that unimodal treatment might not completely alleviate symptoms will further build patient trust. Figure 3 demonstrates our proposed diagnostic algorithm for those presenting with potential DCS symptoms. Future studies that strengthen our understanding of diagnostic tools may refine this algorithm to help guide clinicians.

Figure 3.

Diagnostic flow chart for potential presentations of DCS. Blue arrows indicate findings suggestive of a proximal lesion. Red arrows indicate findings suggestive of a distal lesion. Purple arrows indicate findings suggestive of DCS.

Note. DCS = double crush syndrome.

Treatment and Outcomes

Treating DCS is imperative for patient livelihood. If left untreated or treatment is delayed, patients may experience worsening symptoms, long-term nerve damage, reduced function, and decreased patient reported outcomes. ³ A more detailed classification of the disease would aid in guiding diagnostic workup and prompt treatment, thereby minimizing misdiagnosis-associated mortality. The treatment of DCS should start conservatively with nonsurgical options such as bracing, therapy, avoidance of aggravating factors, medications such as nonsteroidal anti-inflammatory drugs or oral steroids, and steroidal injections as appropriate for each nerve lesion.^1,4 Despite conservative measures being first-line treatment, most studies focus on surgical management and associated outcomes of DCS, without consensus. There remains disagreement regarding the priority of treatment modality as well as surgical results.

Hsiao et al ²¹ support a surgical approach in treating DCS; their retrospective study of patients (n = 21) with concurrent CTS and pronator syndrome demonstrated that surgical interventions, including arthroscopic release and open decompression, led to significant alleviation of pain and paresthesia in most cases. Roughly 71% of patients reported complete resolution with greater than 85% improvement in strength. ²¹ Both Ochoa-Cacique et al ³ and Cohen et al ⁴ also endorse a surgical treatment that simultaneously addresses both nerve lesions present in DCS. Cohen et al ⁴ postulate that treatment should be multifactorial in addressing DCS, as they hypothesize that systemic disease often contributes to DCS and necessitates that treatment address both the systemic disease along with the more focal neuropathy. Ochoa-Cacique et al ³ concur, reporting that of the 32 patients in their study, those receiving bimodal decompression of multiple nerve lesions exhibited the best outcomes. The bimodal decompression patients exhibited the greatest reduction of neuropathic pain scores with significantly improved sensory and motor conduction velocities and larger improvements in quality of life. ³

Others reported different outcomes, finding that carpal tunnel release (CTR) alone left patients with the least postoperative disability. ⁴² Stoy et al ⁴³ analyzed the outcomes of 477 patients who had undergone either anterior cervical decompression and fusion (ACDF, n = 117), CTR (n = 203), or both within 5 years (DCS group, n = 157). Patients who had undergone ACDF alone had the worst functional outcomes when compared to the DCS and CTR groups. Carpal tunnel release patients had the least disability but higher reported arm pain when compared with the DCS group. ⁴³ Moreover, Wessel et al found that patients in their DCS group subjectively had worse outcomes than patients with isolated, peripheral neuropathies. They noted no significant difference in DCS outcomes based on the order of the proximal and distal surgeries. ⁴⁰ Conversely, Baba H et al ²³ suggested treating the cervical lesions first to prevent future complications but noted no objective differences in nerve conduction velocity or physical examination findings when comparing the order of DCS surgeries.

Conclusion

This review analyzes the current literature about DCS, including pathophysiological theories, incidence and epidemiology, current diagnostic strategies, and treatment modalities and outcomes. Despite recognizing the challenges with DCS, studies have not been able to make significant progress in understanding DCS in recent years. Our work has highlighted many gaps in the true incidence of DCS and its diagnostic algorithm, leading to improper expectation setting for its extensive treatment options. A classification of DCS that attributes estimated weights of peripheral versus distal lesions that are contributing to symptomatology could help provide diagnostic clarity and aid in treatment sequence decisions. Larger, collaborative, and prospective studies are necessary to identify a single definition for DCS, address gaps in diagnostic criteria, understand priority of treatment modality, and determine treatment results.