Keywords
double crush syndrome - median nerve - carpal tunnel - neuropathy
Palavras-chave
síndrome do duplo impacto - nervo mediano - túnel do carpo - neuropatia
Introduction
Double crush syndrome (DCS) refers to the coexistence of a double compression along
the course of the same peripheral nerve.[1]
[2] A hypothesis proposed in 1973 by Upton et al describes the potential susceptibility
of a distal nerve segment to lesion after a proximal injury.[1]
[3] It also emphasizes that the damage produced by double compression exceeds the additive
injury caused by each compression, harming the global functioning of the nerve cells.[4]
[5]
This hypothesis can explain why patients with carpal tunnel syndrome (CTS) sometimes
feel pain in the forearm, in the elbow, in the arm, in the shoulder, in the chest,
and in the upper back region.[1]
[6] The DCS also can explain some cases of surgical failure, when the isolated CTS treatment
did not result in pain control.[1]
[6] The DCS manifests as a disorder including pain, numbness and weakness due to two
or more insults to the same peripheral nerve.[3]
[7] When it involves the median nerve, the coexistence of CTS and of cervical radiculopathy
is the most frequent DCS pattern.[2]
[4]
CTS affects ∼ between 3 and 4% of the general population, with a prevalence of female
patients in a 5:1 ratio, and in ages ranging from 30 to 60 years old.[8]
[9]
[10] The incidence of cervical radiculopathy appears to be in < 1% of the population,
often with a peak at the ages between 50 and 54 years old.[11]
[12]
[13]
In view of these issues, the present study aims to describe the epidemiological aspects,
the risk factors, and the histopathological mechanisms involved in the DCS.
Methodology
The present study is a bibliographic review based on the specialized literature, and
it was performed through the consultation of selected scientific papers at the PubMed
database. To prepare the present work, the search used the descriptors double crush syndrome and median nerve. Only papers with patients presenting median nerve compression were included. Papers
on distal compression of the median nerve with no CTS involvement were excluded.
Discussion
Carpal tunnel syndrome is the most frequent compressive syndrome, and it is defined
by the compression of the median nerve at the level of the wrist. Its first description
is assigned to Paget, who reported a case of medial nerve compression as a result
of a distal radius fracture.[14]
The carpal tunnel is an inextensible osteofibrous tunnel defined as the space between
the flexor retinaculum (FR), which constitutes its roof, and the carpal channel, which
constitutes its fundus. It is delimited at the ulnar border by the hook of the hamate
bone, the pyramidal bone and the pisiform bone, and at the radial border by the scaphoid
bone, the trapezoid bone, and the FR. Its base is formed by the capsule, and the anterior
radiocarpal ligaments cover the underlying portions of the scaphoid, semilunar, capitate,
hamate, trapezium and trapezoid bones.[15] The median nerve is followed by four tendons of the digital flexor superficial muscles
(FSD), four tendons of the digital deep flexor muscles (FPD), and by the tendon of
the long flexor muscle of the thumb (FLP).[15] The FLP is the most radial element. At the entrance of the tunnel, the median nerve
is dorsal to the tendon of the palmaris longus (PL) muscle, between the carpal radial
flexor tendon (FCR) and of the digital superficial flexor tendon (SDFT).[15] At the distal part of the tunnel, the median nerve is divided in lateral, medial
and thenar recurrent branches; the former two branches subdivide further.[15] The thenar branch passes through a separate tunnel before entering the thenar muscles
in 56% of the cases.[15]
Typical CTS symptomatology is manifested by pain, hypoesthesia and paresthesia in
the sensory innervation territory of the median nerve and, in some cases, by paresis
for thumb opponency and abduction, as well as by signs of thenar hypotrophy.[2]
The differential diagnosis should include C6 and C7 vertebrae radiculopathy, proximal
medial nerve compressions in the arm (Struthers ligament) or in the forearm (pronator
syndrome), and double impact syndrome. Less frequently, upper motor neuron disease,
cervical intraradicular injuries, neuropathies, and syringomyelia can be considered
in the differential diagnosis.[2]
As already discussed, DCS is postulated as the compressive involvement of more than
one point of the same peripheral nerve. In median nerve DCS, this can be exemplified
by the compression of a spinal nerve—which will contribute to the formation of the
median nerve at the brachial plexus level—and by the presence of an injury at a distal
point of the same nerve, especially in the carpal tunnel.[1]
The prevalence of DCS in CTS patients, cumulated with cervical radiculopathy, varies
greatly in the medical literature. Some studies report a 5% prevalence, while others
state that 94% of the studied patients are affected.[16]
[17]
[18] This extensive variation could be partially explained by the lack of a gold standard
for the diagnosis of DCS.[16]
[17]
[18] Some aspects, however, can be pointed out, such as the higher prevalence in males,
according to studies by Tian et al.[19]
Different physiopathological mechanisms for DCS were suggested, and can be divided
into highly plausible (1–4) and plausible.
-
Axonal transport: Animal studies revealed that axonal transport is compromised by
the mechanical pressure on the nerve at levels commonly observed in humans.[16]
-
Super-regulation and under-regulation of ion channels: The super-regulation of sodium
channels and the under-regulation of potassium channels are observed at points adjacent
to the nerve compression site and could lead to a reduction in the neuronal action
potential threshold.[16]
-
Inflammatory process in the spinal nerve sensory ganglion: The mechanical compression
process of the spinal nerve would lead to the invasion of its sensory ganglion by
immune cells. This process would trigger the release of cytokines that would lower
the threshold to initiate action potentials in sensory neurons located at the sensory
ganglion.[16]
-
Neuromas-in-continuity: Mechanical lesions on a peripheral nerve with an intact epineurium
could lead to a defective regeneration of axon fibers in such a way that, during this
process, they could not reach the peripheral target, forming neuromas along the nerve
trunk.[16]
-
Central sensitization: The nerve compression process would lead to central sensitization,
promoting membrane excitability changes that would reduce inhibition, causing a reduction
in the pain thresholds.[16]
-
Nerve biomechanical aspects and movement patterns: During the movement of the limbs,
the nerve slides over the adjacent tissue in longitudinal and transverse directions.
Disturbances, such as a mechanical compression, could increase distal tension, compromising
the biomechanics of the nerve.[16]
-
Cognitive, psychological and psychosocial factors: Fear or hypervigilance states would
reduce pain thresholds in these patients.[16]
-
Peripheral nerve and spinal cord immunoinflammation: Immunoinflammatory processes
at different points of the nervous system could reduce the action potentials thresholds
of sensory neurons.[16]
-
Microcirculation damage: The nerve compression would affect the microcirculation of
the nerve, resulting in intraneural and extraneural edema.[16]
-
Combined mechanisms: This theory tries to explain DCS through a sum of the aforementioned
mechanisms.[16]
The risk factors for DCS include conditions that predispose patients to CTS and cervical
disc herniation. The risk factors for CTS include diabetes mellitus, alcohol abuse,
amyloidosis, rheumatoid arthritis, infectious synovitis, gout, dermatomyositis, scleroderma,
hypothyroidism, long-term hemodialysis, obesity, repeated wrist flexion-extension
movements, extended wrist during loaded movements, and fist injuries.[20] The risk factors for cervical disc herniation include smoking, cumulative effect
of spine microtraumas and macrotraumas, and osteoporosis.[21] It is noteworthy that some studies point to the male gender and increased age as
independent risk factors for DCS.[22]
The specific symptomatology observed in DCS patients are CTS symptoms plus pain and
cervical region, shoulder and upper limb hypoesthesia ipsilateral to the nerve compression.[23]
The electromyographic changes observed in DCS are more pronounced than those present
in CTS alone. A study comparing electroneuromyography (ENM) findings in patients with
only CTS or DCS (CTS plus cervical radiculopathy) shows that the latter present lower
sensory and motor nerve conduction velocity and higher distal motor latency. Importantly,
these ENM differences were statistically significant.[23]
Although there are specific diagnostic criteria for CTS, they are yet to be established
for DCS.[13]
[24] The diagnosis of cervical radiculopathy is determined by the clinical history of
the patient and imaging tests, such as cervical X-rays, which can show cervical osteophytosis,
as well as computed tomography (CT) and magnetic resonance imaging (MRI) exams.[25]
[26] For some authors, the history of the patients, signs such as Phalen or Tinel-Hoffmann,
and the presence of thenar hypotrophy can be very relevant.[27]
[28] These clinical tests serve as screening tools for an electroneuromyographic study,
which is considered the gold standard for the diagnosis of CTS.[23]
[28]
Regarding the most appropriate surgical treatment for DCS patients, some inferences
can be suggested from studies with CTS patients with unsatisfactory postprocedural
pain control.[4]
[29] The isolated surgical treatment of the distal compression did not provide pain control
if there was a proximal compression of the median nerve. Eason described 47 CTS surgeries
with unsatisfactory outcomes for pain control.[4]
[29] In 38 of these procedures, it was possible to identify an intervertebral foramen
stenosis at the cervical level.[4]
[29]
Two remaining issues would be the best course for DCS patients, and which nerve compression
point should be initially approached in surgery. Baba et al reviewed the medical records
of 483 patients, from which 65 showed peripheral and cervical signs and symptoms,
being classified as DCS carriers.[23]
[25] These authors suggest that the decompression of the cervical spinal nerve should
be initially performed to reduce myelopathy risks due to cervical disc herniation.[23] As such, later, the patient would be submitted to CTS treatment.[23]
Conclusion
Although DCS is recognized as a distinct clinical entity, the exact operation of its
neurophysiological and cellular mechanisms is not yet sufficiently known and universally
accepted. Some patients with CTS can be DCS carriers. There is no consensus regarding
the median nerve site that should be initially decompressed. Further studies are required
in order to better document the physiopathology and the most efficient treatment for
this condition.
