The Double Crush Nerve Syndrome Often Overlooked As A Possible Answer

In 1973, physicians Adrian Upton and Alan McComas introduced a concept suggesting that undiagnosed cervical spine problems could increase the incidence of extremity peripheral entrapment syndromes. They referred to this new concept as the:

Double Crush in Nerve-Entrapment Syndromes

Drs. Upton and McComas published their initial study on this Double Crush Nerve-Entrapment Syndrome in the journal The Lancet, August 18, 1973 (1). Since the introduction of this Double Crush Syndrome concept, numerous studies have supported it, and are reviewed below.

In their original article, Drs. Upton and McComas performed a comprehensive electromyographic study of 115 patients with carpal-tunnel syndromes and lesions of the ulnar nerve at the elbow. In 81 cases (70%) they found electrophysiological evidence, often supported by clinical symptoms, of associated neural lesions in the neck. They concluded that the association between carpel-tunnel syndromes, elbow ulnar nerve lesions, and electrophysiological abnormalities of the cervical spine were not “fortuitous, but rather the result of serial constraints of axoplasmic flow in nerve fibers.”

Drs. Upton and McComas note that in carpal tunnel syndrome, fibers of the median nerve are compressed beneath the transverse carpal ligament.

At surgery the median nerve can be seen:

1) To be flattened or narrowed

2) To be swollen and pink

3) To have thickened synovial sheaths around the wrist flexor tendons

Precipitating factors to developing carpal tunnel syndrome include:

1) Heavy manual work

2) Obesity

3) Diabetes

4) Rheumatoid arthritis

5) Prior wrist injury

However, many patients who develop carpal tunnel syndrome have none of these classical precipitating factors. Drs. Upton and McComas note that:

“Many patients with clinical and electromyographic evidence of a carpal tunnel syndrome feel some pain in the forearm, elbow, upper arm, shoulder, and front and back of the chest.”

Upton and McComas make an argument why these symptoms may not be referred from the wrist, as they are commonly believed to be, but rather represent symptoms that are proximal, especially from lesions in the cervical spine. They note:

“Not all patients lose the numbness in their fingers or regain strength in their thenar muscles after surgical decompression of the median nerve” even though the diagnosis was correct and the surgical decompression was adequate.

Additionally, at times, the severity of symptoms is not proportional to the compressive pathology seen at surgery. They cite a surgical study of carpal tunnel syndrome where 29% (61/212) of the nerves showed no evidence of compression.

In their 1973 study, “in no fewer than 81 (70%) of the 115 patients with an electrophysiological-proven entrapment neuropathy there was evidence of a cervical root lesion.”

The evidence for cervical root lesion included:

1) Radiological evidence of cervical spondylosis.

2) Complaints of neck pain and stiffness.

3) “A previous history of neck injury, commonly of the hyperextension ‘whiplash’ type sustained in a rear-end motor vehicle accidents.”

4) “Clinical evidence of a sensory abnormality corresponding to a dermatomal rather than a peripheral nerve distribution.”

5) Electromyographic evidence of denervation of other muscles that are supplied by the nerve root.

Drs. Upton and McComas state:

“Most patients with carpal tunnel syndromes or ulnar neuropathies not only have compressive lesions at the wrist or elbow, but they also have evidence of damage at the level of the cervical roots.”

A cervical lesion would explain the presence of pain in the shoulder and upper arm, the variable nerve pathology seen at the wrist, and the surgical failure of cases with adequate wrist nerve decompression. Neural function is impaired because “single axon compression at one region becomes especially susceptible to damage at another [peripheral] site.” Slight degrees of nerve compression may cause no symptoms, but reduce the axoplasmic flow of trophic substances, so that a slight distal compression may add to the reduction of axoplasmic flow of trophic substances, causing symptoms.

Even though Drs. Upton and McComas refer to such a phenomenon as a “double crush,” they “accept” that “in some patients, especially those with a history of neck injury, the proximal lesion may have been excessive stretch, rather than compression, of the nerve fibers.”

Drs. Upton and McComas end their study by noting:

“Treatment, rather than being directed at a single site, should be applied to all vulnerable points along the course of the nerve—i.e., to both the neck and to the wrist or elbow, depending on the nerve involved.”

The Double Crush Nerve-Entrapment Syndrome is an important concept for all providers that treat peripheral entrapment syndromes, such as carpel tunnel syndrome. It indicates that a majority of such patients may also have proximal neurological lesions that also require treatment, starting at the level of the cervical nerve roots. A summary of the key points from this study by Drs. Upton and McComas include:

1) The DOUBLE CRUSH SYNDROME is: serial constraints of axoplasmic flow in nerve fibers increasing the susceptibility of distal axons, of that nerve, to compression syndromes and symptomatology.

2) Surgical decompression of the wrist clearly does not fix all the patients with carpal tunnel syndrome.

3) In this study, 70% of the patients with an electrophysiological-proven entrapment neuropathy had evidence of a cervical nerve root lesion.

4) The most common history for those with a double crush syndrome is that of “A previous history of neck injury, commonly of the hyperextension ‘whiplash’ type sustained in a rear-end motor vehicle accident.”

5) The most common non-local complaint for those with a double crush syndrome is neck pain and stiffness.

6) The most common examination finding for those with a double crush syndrome is evidence of cervical spondylosis.

7) “Most patients with carpal tunnel syndromes or ulnar neuropathies not only have compressive lesions at the wrist or elbow, but they also have evidence of damage at the level of the cervical roots.”

8) Even though these authors refer to such a phenomenon as a “double crush,” they “accept” that “in some patients, especially those with a history of neck injury, the proximal lesion may have been excessive stretch, rather than compression, of the nerve fibers.”

9) In the treatment of peripheral neuropathies (such as carpal tunnel syndrome) “treatment, rather than being directed at a single site, should be applied to all vulnerable points along the course of the nerve—i.e., to both the neck and to the wrist or elbow, depending on the nerve involved.”

In 1975, the International Conference on the Approaches to the Validation of Manipulation Therapy was held at the University of California, Irvine.

••••••

renowned international spinal experts contributed to the conference. The Proceedings from the conference were published in 1977 (2). Chapter 7 of the book is authored by Dr. Adrian Upton, one of the originators of the Double Crush Hypothesis. In his chapter, Dr. Upton restates his Double Crush Hypothesis as follows:

“Serial lesions along the course of nerve axons may predispose to nerve damage more distally, possibly by serial constraints on axoplasmic flow; hence the proximal symptoms in a patient with carpal tunnel syndrome may be due to nerve root impairment which has predisposed them to a distal entrapment neuropathy.”

And

“Serial constraints on axoplasmic flow may be responsible for increasing the susceptibility of nerve axons to distal impairment.”

In his discussion, Dr. Upton includes not only the median nerve as related to carpal tunnel syndrome, but also extends his discussion to include the ulnar nerve as well as the sciatic nerve.

More than a decade after the original study of the Double Crush Nerve-Entrapment Syndrome by Drs. Adrian Upton and Alan McComas, a follow-up study was published in the British Journal of Hand Surgery, titled (3):

The relationship of the double crush to carpal tunnel syndrome
(an analysis of 1,000 cases of carpal tunnel syndrome)

In this study, the authors reviewed 1,000 cases of carpal tunnel syndrome and found that in 888 patients (89%), “there is a statistically significant incidence of bilaterality in patients with cervical arthritis.” They note that their findings “lend further support to Upton’s Double Crush hypothesis.”

Additionally, these authors note that in those suffering from the double crush syndrome subsequent to cervical spine lesions, there is an increased probability that the carpel tunnel syndrome will exist bilaterally. They also note that bilateral carpel tunnel syndrome subsequent to cervical spine Double Crush is associated with a worse prognosis for clinical recovery. This may be an explanation for some of the failures following carpal tunnel surgery, and surgeons to look for associated mechanical blocks (Double Crush Syndrome), “when attempting to alleviate recalcitrant symptoms.”

This article also makes a special note of the finding that systemic diseases, especially diabetes mellitus, can predispose an individual to both peripheral entrapment syndromes as well as to “Double Crush Syndromes.”

Three years later, in 1988, Dr. Osterman from the Hospital of the University of Pennsylvania, Philadelphia, published in the journal Orthopedic Clinics of North America an article titled (4):

The Double Crush Syndrome

In this article, Dr. Osterman makes the following points:

• “Multilevel lesions along a peripheral nerve trunk do occur.”

• “In the double crush syndrome as postulated by Upton and McComas, the presence of a more proximal lesion does seem to render the more distal nerve trunk more vulnerable to compression.”

• “While the exact pathophysiologic mechanism of this interaction is not yet elucidated, it most likely relates to disturbances in axonal flow kinetics and the disruption of the neurofilament architecture.”

• “On a practical level our studies show that given a more proximal root compression less involvement of the median nerve across the carpal tunnel was required to produce symptoms.”

• “Furthermore, the surgical outcome of carpal tunnel release in this double crush group was poorer than in that group with isolated carpal tunnel involvement.”

• “It is important to preoperatively identify those patients who may have double crush lesions and thus anticipate a less than optimal result from surgical release of the peripheral nerve.”

• “When the double crush syndrome is present, both entrapments may require treatment for optimal results.”

This article adds to the literature supporting the existence of a double crush peripheral nerve entrapment syndrome. Additionally, this author stresses the need to treat the proximal neurological lesion in an effort to achieve maximum benefit of peripheral management, including surgery. In essence, if the cervical spine is involved in a double crush capacity, it should be appropriately treated.

Primary experimental evidence to support the double crush hypothesis was presented in 1991 (5) by Drs. Dellon and Mackinnon from the Division of Plastic Surgery, Johns Hopkins University School of Medicine, Toronto, Ontario, Canada. Their paper was published in the Annals of Plastic Surgery, and titled:

Chronic nerve compression model for the double crush hypothesis

In this article, Drs. Dellon and Mackinnon make the following points:

• “’Double crush hypothesis’ is a phrase that has entered clinical use based on a hypothesis presented by Upton and McComas in 1973.”

• “Although clinical examples of the double crush are appearing more frequently, there has been no experimental proof of this hypothesis as it relates to chronic nerve compression.”

• “This study used a model of sciatic nerve minimal banding in the rat to investigate the effect on electrophysiological function of single or double band placement, concurrently or separated in time.”

• “This study confirms that the existence of two sites of simultaneous compression, or a second (later) site of compression, placed either proximal or distal to the first (earlier) site of compression, will result in significantly poorer neural function than will a single site of compression.”

This experimental animal study is the first to offer viable evidence that there is a scientific basis for the Double Crush Syndrome that had been used to describe observations on human subjects.

In 1994, Drs. Raps and Rubin from the Department of Neurology, Hospital for Special Surgery, New York, NY, published an article that consisted of two case studies of proximal median neuropathy associated with cervical radiculopathy which they diagnosed in their EMG laboratory. Their paper was published in the journal Electromyography and Clinical Neurophysiology (6), and titled:

Proximal median neuropathy and cervical radiculopathy:
double crush revisited

In their paper, Drs. Raps and Rubin note:

• “’Double crush’” refers to the hypothesis that a single lesion along the course of a nerve predisposes that nerve to a second lesion further along its course.

• “Considering the extreme rarity of proximal median neuropathy, its association in both cases with cervical root disease supports the notion that the cervical radiculopathy may have predisposed the nerve to a second lesion along its course, resulting in the so called double crush syndrome, and that this syndrome may therefore be a true entity.”

In 1999, Drs. from St. Mary’s Hospital associated with Yale University School of Medicine in Waterbury, CT, presented two cases of nerve compression consistent with the Double Crush Syndrome. Their paper was published in Connecticut Medicine (7), and titled:

The double-crush phenomenon:
an unusual presentation and literature review

As noted, in their review of the literature, the authors made the following points:

• “The double-crush syndrome was initially described by Upton and McComas in 1973.”

• “They postulated that non-symptomatic impairment of axoplasmic flow at more than one site along a nerve might summate to cause a symptomatic neuropathy.”

• “This was suggested by their clinical observation that the majority of their patients had a median or ulnar neuropathy associated with evidence of cervico-thoracic root lesions.”

• “Other researchers have since reported series of patients supporting the frequent association of a proximal and distal nerve compression syndrome, including carpal tunnel syndrome associated with cervical radiculopathy, brachial plexus compression, and diabetic neuropathy.”

Importantly, this 1999 article reiterates the relevance of cervical and/or thoracic spinal problems adversely affecting the nerve roots as contributing to the peripheral double crush phenomenon. It also reiterates the issue of systemic metabolic problems, such as diabetes.

More recently, in 2003, Drs. Pierre-Jerome and Bekkelund from the Department of Radiology, Ulleval University Hospital, Oslo, Norway, published a study in the Scandinavian Journal of Plastic and Reconstructive Hand Surgery (8), and titled:

Magnetic resonance assessment of
the double-crush phenomenon in patients with
carpal tunnel syndrome: a bilateral quantitative study

In this paper, Drs. Pierre-Jerome and Bekkelund assessed the coexistence of narrowed cervical foramens and cervical canal stenosis in patients with carpal tunnel syndrome (CTS). They took magnetic resonance (MR) images of 120 wrists and 480 foramens in 60 age and sex matched subjects: 30 patients with CTS and 30 controls without CTS. For each subject, the authors performed nerve conduction velocity tests, measured the volume of the carpal tunnel canal bilaterally, quantified the cross-sectional areas of the cervical foramens on both sides from C4 to T1, measured the diameter of the cervical central canal, and documented the prevalence and location of cervical spondylosis and disc prolapse.

The authors concluded “there was no correlation between the symptoms and the reduced carpal canal volume.” However, cervical spondylosis and disc prolapse were more common in the patients than the controls at the C5-C6 and C6-C7 levels, and their locations were usually on the same side as the symptoms in the wrist(s). Therefore, they concluded:

“The higher incidence of narrowed cervical foramens in the patients and its concordance with affected nerve roots on the same side as the CTS symptoms support the hypothesis of a double-crush phenomenon.”

Importantly, this study adds to the evidence that cervical spine spondylosis,

disc degenerative disease, and disc prolapse, increase the incidence of peripheral neuropathy at the wrist. This adds to the perspective that in patients with peripheral neurological problems, especially at the wrist, the cervical spine should be examined and appropriately treated if consistent findings are found.

Two years ago, in 2006, Drs. Flak, Durmala, Czernicki and Dobosiewicz, from the Department of Medical Rehabilitation, School of Healthcare, Medical University of Silesia, Katowice, Poland, published a study in the journal Studies in Health Technology Information, titled (9):

Double crush syndrome evaluation in the median nerve in clinical, radiological and electrophysiological examination

In this study, the authors evaluated the Double Crush Syndrome hypothesis of the median nerve on the basis of available diagnostic methods. Specifically, they examined 30 patients with coexisting carpal tunnel syndrome (CTS) and cervical radiculopathy (CR), along with a control group that consisted of 40 healthy volunteers. The medical evaluation comprised clinical examination, X-ray and MR imaging of the cervical spine, electroneurography (ENG) with F-wave and somatosensory evoked potentials (mSEPs) of median nerves.

In clinical examination 96.6% of patients suffered from cervical spine pain and nocturnal paresthesies of at least one hand. Muscular atrophy was present in 43.3% in the proximal and in 70% in the distal part of the upper extremity. 30.3% of patients presented with a thoracic scoliosis.

On X-ray examination, all patients showed cervical discopathy, mostly C5-C6

(70%) and C6-C7 (53.3%).

On MR investigation, the narrowing of intervertebral foramina was present in

81.25%, and narrowing of central vertebral canal was present in 37.5%.

On ENG all patients presented with CTS, and it was bilateral in 73.3%.

The F wave was abnormal in 73.3% and mSEPs in 66.7% of patients. The

coincidence of MR and mSEPs in view of lateralization was found in 71.4%. Based upon the results of this study, these authors concluded:

• “Double crush syndrome was first described by Upton and McComas who proposed that focal compression of an axon often occurs at more than one level.”

• “Results [from this study] supported the Double Crush Syndrome hypothesis.”

• “Double Crush Syndrome evaluation requires both structural and functional diagnosis of peripheral neurons using MRI and electrophysiological examination.”

Once more, evidence is presented supporting the concept that cervical

spine structural problems can adversely affect the exiting nerve roots, increasing the incidence of peripheral entrapment neuropathy. These authors note that the best structural evaluation of the cervical spine in these suspected Double Crush cases is magnetic resonance imaging of the cervical spine.

In a study published earlier this year (January 2008), Smith, Sawyer, Sizer, and Brismee, from the Center of Rehabilitation Research, Texas Tech University Health Sciences Center, Lubbock, Texas, evaluated the incidence of Double Crush as related to ulnar nerve neuropathy in a group of cyclists. They published their work in the Clinical Journal of Sports Medicine, titled (10):

The double crush syndrome: a common occurrence in
cyclists with ulnar nerve neuropathy: a case-control study

In this study, the authors evaluated the incidence of double crush syndrome

in the upper limbs of 70 cyclists (140 upper limbs) with clinical diagnosis of ulnar nerve neuropathy. The cyclists were examined clinically for the presence of proximal neurological dysfunction using the following testing:

(1) Thoracic outlet syndrome provocation testing

(2) Documenting the presence of an elevated first rib

(3) Documenting the presence of proximal symptoms, such as reports of neck pain and shoulder pain.

The results of their study showed a significantly greater number of upper limbs of cyclists with ulnar nerve neuropathy presented with positive provocative testing for thoracic outlet syndrome than did the upper limbs of cyclists without ulnar nerve neuropathy.

Cyclists with ulnar nerve neuropathy were three times more likely to have

neck pain, five times more likely to have shoulder pain, and twelve times more likely to have an elevated first rib as compared to the group that did not have an ulnar nerve neuropathy.

These authors concluded:

“A statistically significant greater number of the upper limbs of cyclists with clinical diagnosis of ulnar nerve neuropathy presented with proximal dysfunctions suggestive of double crush syndrome.”

Importantly, this study not only adds to the evidence supporting a double

crush mechanism in peripheral neuropathy, but it specifically adds that thoracic outlet is a viable location for the proximal lesion. This would argue that in patients with peripheral neuropathy, both the cervical spine and the thoracic outlet should be thoroughly examined, even potentially be subject to diagnostic imaging, when evaluating patients with peripheral compressive neuropathy.

Also in January of this year (2008), Drs. Moghtaderi, Izadi, from the Neurology Department, Zahedan University School of Medicine, Khatam Teaching Hospital, Zahedan, Iran, published a paper in the journal Clinical Neurology and Neurosurgery titled (11):

Double crush syndrome:
an analysis of age, gender and body mass index

In this study, these authors evaluated the role of age, gender, body mass index (BMI), wrist ratio and median sensory nerve conduction velocity as independent risk factors for double crush syndrome. They used 142 patients with carpal tunnel syndrome (CTS) and 109 controls.

The results of this study showed that increasing age and male gender increased the probability that patients with carpal tunnel syndrome would also have a double crush component. The authors concluded:

“Our study confirms that male gender and increased age are independent risk factors for Double Crush Syndrome.”

These authors also suggested that in elderly men presenting with CTS, electrophysiologic screening for cervical radiculopathy should be considered because the treatment of Double Crush Syndrome CTS differs from the treatment for pure CTS.

CONCLUSIONS

The basic premise of the Double Crush Syndrome, as succinctly stated by Dr. Adrian Upton in 1977 (2), is:

“Serial constraints on axoplasmic flow may be responsible for increasing the susceptibility of nerve axons to distal impairment.”

Studies supporting the existence of the Double Crush Syndrome have appeared in the literature for 35 years. Most studies supporting the existence of the Double Crush Syndrome pertain to the cervical spine and the upper extremity, primarily to the median nerve and carpal tunnel syndrome. The “serial constraints” mentioned by Dr. Upton in 1977 include metabolic disorders (primarily diabetes), stretch injuries or chronic nerve stretch, and compressive disorders. Most importantly, and as succinctly stated by Drs. Upton and McComas in the original study in 1973 (1):

“Treatment, rather than being directed at a single site, should be applied to all vulnerable points along the course of the nerve—i.e., to both the neck and to the wrist or elbow, depending on the nerve involved.”

Recognition that patients with symptoms and diagnosis of peripheral entrapment neuropathy often have proximal contributing lesions in the spine is important. Treatment of the spinal problems in such patients will improve clinical outcomes.

References

1) Upton A and McComas A; The Double Crush in Nerve-Entrapment Syndromes; The Lancet; August 18, 1973, pp. 359-362.

2) Buerger AA and Tobis JS, editors; Approaches to the Validation of Manipulation Therapy; Thomas; 1977.

3) Hurst LC, Weissberg D, Carroll RE; The relationship of the double crush to carpal tunnel syndrome (an analysis of 1,000 cases of carpal tunnel syndrome);

Journal of Hand Surgery [British]; June 1985;10(2):202-4.

4) Osterman AL; The double crush syndrome; Orthopedic Clinics of North America; January 1988;19(1):147-55.

5) Dellon AL, Mackinnon SE; Chronic nerve compression model for the double crush hypothesis; Annals of Plastic Surgery; March 1991;26(3):259-64.

6) Raps SP, Rubin M; Proximal median neuropathy and cervical radiculopathy: double crush revisited; Electromyography and Clinical Neurophysiology; June 1994;34(4):195-6.

7) Zahir KS, Zahir FS, Thomas JG, Dudrick SJ; The double-crush phenomenon: an unusual presentation and literature review; Connecticut Medicine; September 1999;63(9):535-8.

8) Pierre-Jerome C, Bekkelund SI; Magnetic resonance assessment of the double-crush phenomenon in patients with carpal tunnel syndrome: a bilateral quantitative study; Scandinavian Journal of Plastic and Reconstructive Hand Surgery; 2003;37(1):46-53.

9) Flak M, Durmala J, Czernicki K, Dobosiewicz K; Double crush syndrome evaluation in the median nerve in clinical, radiological and electrophysiological examination; Studies in Health Technology Information; 2006;123:435-41.

10) Smith TM, Sawyer SF, Sizer PS, Brismée JM; The double crush syndrome: a common occurrence in cyclists with ulnar nerve neuropathy-a case-control study; Clinical Journal of Sport Medicine; January 2008;18(1):55-61.

11) Moghtaderi A, Izadi S; Double crush syndrome: an analysis of age, gender and body mass index; Clinical Neurology and Neurosurgery; January 2008;110(1):25-9.

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