Double Crush Syndrome

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Double crush syndrome (DCS) is a clinical condition characterized by the compression of a single peripheral nerve at two or more distinct locations along its course, clasically one at the nerve root level and a second lesion peripherally most commonly at the carpal tunnel. The concept was first introduced in 1973 by Upton and McComas, who observed a high prevalence of cervical radiculopathy in patients with carpal tunnel syndrome (CTS) or ulnar neuropathy at the elbow. The core of their hypothesis is that compression at a proximal site impairs the axoplasmic flow within the nerve, rendering the distal portion of the nerve more susceptible to a second, more distal compression.

While the classic definition focuses on serial mechanical compression, the understanding of this phenomenon has evolved. Controversy surrounds not only the underlying mechanisms but also the very existence of the syndrome as a distinct clinical entity. The reported incidence varies widely, and there is no consensus on a definitive diagnostic test. In recent years, the term multifocal neuropathy (MFN) has been proposed as a more encompassing term. This concept expands upon the purely mechanical definition of DCS to include the synergistic effects of systemic diseases (e.g., diabetes), metabolic disorders, and pharmacological factors, which can also compromise nerve function and contribute to the clinical presentation.

Epidemiology and Incidence

The true incidence of DCS remains uncertain, largely due to the lack of standardized diagnostic criteria. Studies report a wide range of incidence, from less than 1% to over 70%, depending on the population studied and the criteria used.

The original study by Upton and McComas found that 70% of 115 patients with either CTS or ulnar neuropathy had electrophysiological or clinical evidence of an associated lesion in the neck. Subsequent studies have produced conflicting results. A retrospective review by Morgan and Wilbourn, which applied strict clinical and electrodiagnostic criteria, found that the incidence of concomitant CTS or cubital tunnel syndrome with cervical radiculopathy was less than 1%. In contrast, a large, recent retrospective database study by Mills et al. on surgically treated patients found the incidence to be more substantial. They reported that among patients with cervical radiculopathy, 9.98% had concomitant CTS and 3.15% had peripheral ulnar nerve compression. Conversely, the incidence of cervical radiculopathy was 2.86% in patients with CTS and 5.13% in patients with peripheral ulnar nerve compression.

Risk factors for DCS are also debated. For instance, while CTS is more common in females, some studies have reported that male sex is an independent risk factor for DCS. Others have identified older age and the presence of diabetes as potential risk factors.

Pathophysiology

The pathophysiology of DCS is complex and likely involves multiple mechanisms occurring in combination. While the original theory remains central, recent research has illuminated other plausible biological processes.

Axonal Transport Theory

The foundational theory, proposed by Upton and McComas, posits that nerve function depends on the uninterrupted bidirectional axoplasmic transport of essential nutrients and trophic substances from the neuron cell body (perikaryon) along the axon. A proximal compression (the first "crush") can obstruct this flow, even subclinically. This impairment reduces the nerve's ability to maintain its distal structure and function, thereby increasing its vulnerability to damage from a second, more distal compression. Animal models have supported this synergistic effect, demonstrating that two sites of compression produce a greater functional deficit than the sum of each lesion applied independently.

In addition to the classic theory of impaired anterograde (forward) axoplasmic flow, it's also suggested that impairment of retrograde (backward) flow within the axon can make the proximal part of the nerve more susceptible to compression.

An important critique of this hypothesis is noting the unique anatomy of sensory neurons. Their cell bodies are in the dorsal root ganglia, and anterograde axonal transport occurs in two directions from there, distally into the peripheral nerve and proximally into the nerve root via separate systems.

Cervical radiculopathy is a "crush" on the nerve root - the pipeline between the DRG and spinal cord. Carpal Tunnel Syndrome is a "crush" on a peripheral nerve - the pipeline between the DRG and the hand. According to critics, a crush on the nerve root would primarily disrupt flow leading to the spinal cord, not necessarily the flow leading down tot he wrist due to two separate transport systems.

This anatomical fact is used to argue that the classic DCS axonal transport mechanism has limited application for cases involving cervical radiculopathies.

Newer and Complementary Mechanisms

A Delphi study of international experts identified several other mechanisms that are now considered highly plausible contributors to dual nerve disorders

• Ion Channel Up- or Downregulation: Following a primary nerve injury, there can be an upregulation of sodium channels and a downregulation of potassium channels both proximal and distal to the lesion. This alteration lowers the neuron's firing threshold, increasing its excitability and susceptibility to ectopic firing, which has been linked to neuropathic pain.
• Inflammation of the Dorsal Root Ganglia (DRG): Peripheral nerve injury can trigger an invasion of immune cells into the DRG. These cells release excitatory cytokines that can lower the firing threshold of sensory neurons. Because the cell bodies of both injured and uninjured neurons are in close proximity within the DRG, this inflammation can affect axons originating from sites distant to the primary injury.
• Neuroma-in-Continuity: After an injury where the epineurium remains intact, regenerating axonal sprouts can fail to reach their targets, forming a neuroma-in-continuity. These regenerating axons are known to be more sensitive to mechanical stimuli and exhibit ectopic activity, meaning that normally innocuous stimuli like movement may be sufficient to excite them.
• Central Sensitization: Persistent nociceptive input from a primary nerve lesion can lead to central sensitization, a state of nervous system hyperexcitability involving increased synaptic efficacy and reduced inhibition. This can result in reduced pain thresholds and the spread of pain to unaffected areas, potentially unmasking a secondary, previously subclinical nerve compression site.

The Multifocal Neuropathy (MFN) Concept

The MFN model broadens the scope of DCS beyond purely mechanical factors. It suggests a complex interplay among mechanical, systemic, pharmacological, and environmental factors that synergistically contribute to nerve dysfunction. In this view, systemic conditions such as diabetes, hypothyroidism, chronic kidney disease, or exposure to neurotoxic medications can act as an underlying pathology or a "crush" in themselves, rendering the entire nervous system more vulnerable to focal compressive lesions.

Clinical Presentation and Diagnosis

Diagnosing DCS is challenging, as there is no single pathognomonic sign, symptom, or test. The diagnosis is often one of clinical suspicion, supported by a careful history, a thorough physical examination, and targeted diagnostic studies. It is frequently considered in patients who experience persistent or unresolved symptoms after surgical treatment for a single, isolated neuropathy.

In the upper limb the most common scenario is a C6 cervical radiculopathy plus a carpal tunnel syndrome.

In the lower limb the most common scenario is a L5 or S1 lumbar radiculopathy plus a peroneal nerve for the former or tibial nerve syndrome for the latter.

History and Physical Examination

The clinical presentation is highly variable and depends on the nerves and locations involved. Patients often present with overlapping symptoms from both the proximal and distal sites of compression.

Key clinical clues that may suggest DCS over an isolated neuropathy (e.g., CTS) include:

• Pain Distribution: Pain that radiates proximally from the site of distal compression into the forearm, elbow, upper arm, or shoulder.
• Nocturnal Symptoms: The absence of nocturnal awakening with paresthesia, which is a classic feature of CTS, may suggest a more proximal compression is the primary driver of symptoms.
• Sensory and Motor Deficits: Subjective reports of greater grip strength disability and more widespread paresthesia are more common in DCS patients compared to those with isolated CTS.
• Provocative Maneuvers: Classic provocative tests for distal neuropathies, such as the Phalen's and Tinel's signs for CTS, may be less frequently positive in DCS patients. A comprehensive examination should include tests for proximal compression sites, such as resisted forearm pronation or elbow flexion for proximal median nerve compression, and a thorough cervical spine examination, including Spurling's maneuver. Examination should also assess for signs of myelopathy (e.g., hyperreflexia, Hoffman's sign) versus radiculopathy (e.g., hyporeflexia, dermatomal sensory loss, myotomal weakness).

A specific physical examination technique, the "hierarchical" SCT, can be used for identifying multiple compression sites. In this test, a primary compression site identified by the SCT is temporarily numbed with ethyl chloride, which may then cause the SCT to become positive at a secondary compression site, helping to unmask the "double crush"

Diagnostic Studies

No single diagnostic test can definitively confirm DCS. Instead, a combination of studies is used to identify pathology at multiple sites.

Electrodiagnostic Studies (EMG/NCS): These are a cornerstone of the diagnostic work-up to confirm and localize peripheral nerve compression. However, their sensitivity for detecting proximal median nerve compressions is variable, and many studies report normal findings in a significant number of clinically suspected cases. Furthermore, EMG may not simultaneously detect a proximal lesion when the study is focused on evaluating a distal one.

Imaging:

• Magnetic Resonance Imaging (MRI): MRI is the gold standard for evaluating cervical spine pathology, such as disc herniation or foraminal stenosis. However, degenerative findings on cervical MRI are common in asymptomatic individuals, so imaging results must be carefully correlated with the patient's clinical presentation.
• Ultrasound (US): High-resolution ultrasound is gaining popularity as a non-invasive tool for evaluating peripheral nerves. It can visualize nerve morphology, identify points of compression or swelling, and detect anatomical variants. It can be particularly useful for identifying a second compression site that was not apparent on electrodiagnostic testing. A limitation is that its accuracy is highly operator-dependent. The level of skill required is not routinely available in radiology centres across New Zealand.
• Radiographs: Plain X-rays of the cervical spine or elbow can reveal degenerative changes or bony anomalies (e.g., a supracondylar process) but are generally of limited utility for diagnosing nerve compression directly.

Management Principles

A trial of conservative, non-surgical management is warranted for the vast majority of cases and should be considered the first line of treatment. Treatment may include activity modification, orthoses and bracing, physical therapy, medications, injections.

Surgical intervention should be considered when conservative measures fail after an adequate trial or if there is evidence of progressive neurological deficit. Surgical outcomes for DCS may be less predictable and less complete compared to surgery for an isolated neuropathy. Patients with DCS undergoing carpal tunnel release have worse subjective outcomes than those with isolated CTS.

There is no consensus on whether to address the proximal or distal lesion first, or if they should be addressed simultaneously. Some studies report the best outcomes with bimodal decompression of multiple nerve lesions, while others have found no significant difference in outcomes based on the order of surgery.

The argument for treating the spinal lesion first is because the radiculopathy is neurologically upstream affecting more nerves and muscles. The argument for treating the peripheral nerve first is because of lower morbidity.

In line with the multifocal neuropathy model, it is imperative to identify and manage any underlying systemic diseases that may be contributing to the nerve dysfunction for example obesity, diabetes, nutritional deficiencies, and thyroid disorders.

Resources

Double crush - upton 1973.pdf- 544 KB (f)

Double crush delphi study - Schmid 2011.pdf- 350 KB (f)

Double crush syndrome review - Ghali 2025.pdf- 953 KB (f)

Multifocal neuropathy double crush - Cohen 2016.pdf- 387 KB (f)

Important articles, PDF not available:

• https://www.sciencedirect.com/science/article/abs/pii/S0749071221007228
• https://www.sciencedirect.com/science/article/abs/pii/S0030589820320812
• https://pubmed.ncbi.nlm.nih.gov/8724572/