Chronic inflammatory demyelinating polyradiculoneuropathy
Sep. 05, 2022
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This article includes discussion of carpal tunnel syndrome and median nerve entrapment at the wrist. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.
Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy with a prevalence of about 270 per 100,000. The etiology is compression of the median nerve in the carpal tunnel. Clinical manifestations consist of intermittent pain, numbness, and tingling in the fingers that is dependent on the position of the hand and wrist and commonly associated with subjective weakness of grip. Diagnosis is made on the basis of clinical complaints and electrodiagnostic studies. Treatment is conservative or surgical depending on the severity of the symptoms. Data on carpal tunnel syndrome in pregnancy reveal that about half of the patients remain symptomatic at 6 months after delivery. Ultrasound has emerged as a useful and less invasive technique for evaluation of carpal tunnel syndrome. Endoscopic carpal tunnel release supposedly produces less scarring than open release, but is more expensive and precludes visualization of the median nerve proper. Controversy continues about which surgical procedure is the best. Some studies showed increased prevalence of carpal tunnel syndrome in patients with cardiac amyloidosis. In this article, the author discusses updates on diagnosis and management.
• Carpal tunnel syndrome is the most common entrapment neuropathy.
• Peripheral nerve ultrasound imaging is proposed as a painless rapid screening test for carpal tunnel syndrome.
• Electrodiagnostic studies have a sensitivity of up to 95% for the diagnosis when detailed studies are performed.
• In most patients, including elderly patients and patients with diabetes, surgical carpal tunnel release should be considered if conservative measures fail.
The first description of a chronic median nerve entrapment at the wrist was by Paget (42) concerning a patient with a previous distal radius fracture (49). This was a severe entrapment accompanied by ulceration in the first 3 fingers. Paget noted recovery of the ulcerations with rest and an increase of symptoms with use of the hand secondary to nerve compression. Putnam first described the classical clinical symptoms of intermittent nocturnal hand paresthesias with subjective hand swelling and an improvement with shaking of the hand (46). A careful autopsy study by Marie and Foix documents the thinning of the median nerve under the flexor retinaculum in a patient with bilateral isolated thenar atrophy (33). They made the suggestion that transection of this ligament may have been therapeutic. The first surgery for carpal tunnel syndrome was done in 1933 at the Mayo Clinic. Carpal tunnel syndrome received increasing attention in the 1940s and 1950s from both neurologists and surgeons. The development of clinical electrodiagnostic testing with EMG and nerve conduction studies in the 1960s added a valuable diagnostic tool. The use of high resolution ultrasound imaging to study the median nerve in carpal tunnel syndrome was first published in 1992 (06); however, most studies have appeared since early 2000.
The clinical manifestations of carpal tunnel syndrome consist of intermittent pain, numbness, and tingling in the fingers that is dependent on the position of the hand and wrist and commonly associated with subjective weakness of grip. The symptoms occur initially at night only and may wake the patient from sleep. In a more severe carpal tunnel syndrome the symptoms occur also during the day. They are often provoked by hyperextension or hyperflexion of the wrist during activities such as driving, or during work-related repeated hand movements. The pain can radiate up into the forearm or even up to the shoulder. There frequently is subjective hand swelling and stiffness. The patient will often shake the hand and fingers in an effort to obtain relief from the discomfort (flick sign). Usually, the dominant hand is more involved than the nondominant hand. Although positive sensory symptoms such as pain and tingling predominate, occasionally the only sensory symptom is loss of dexterity. The incidence of carpal tunnel syndrome is highest in middle-aged women. There is also an association with pregnancy.
On clinical examination there can be a discrete sensory disturbance in the first 3 fingers and weakness or atrophy of the thenar muscles with a positive Tinel's sign over the carpal tunnel. Phalen's test, in which the patient hyperflexes the wrist for 1 minute, may provoke the symptoms (45). Alternatively, hyperextension of the wrist for 1 minute may have the same effect. Phalen's test is somewhat more specific for carpal tunnel syndrome than the Tinel's sign but both can be present in normal individuals (18). It is often more the clinical history than the physical examination that is highly suggestive of carpal tunnel syndrome.
The clinical recovery is more pronounced than the electrophysiologic recovery (08). The prognosis for recovery is good with either conservative or surgical treatment; however, surgery is more effective than steroid injection for treatment of moderate carpal tunnel syndrome (08). The complications include persistent weakness and sensory loss in the distal median nerve distribution. The most dramatic complication is complex regional pain syndrome, a condition that is characterized by severe pain, hyperalgesia, dysesthesia, and trophic disturbances.
A 41-year-old female artist presented with a 2-year history of numbness in both hands, right greater than left. The numbness was most severe in the right thumb and was specifically brought on by painting and sculpting. Numbness, pain, and tingling in both hands woke her up at night. Shaking her hands provided some relief. There were no complaints of pain in the shoulder, neck, or upper arm and no history of diabetes mellitus, hypothyroidism, or rheumatoid arthritis.
On neurologic examination, abnormal findings were limited to minimal weakness of the right abductor pollicis brevis muscle and reduced pinprick perception in the right median nerve distribution, maximally on the thumb and the tip of the second and third finger with sparing of the thenar eminence. Phalen's test was positive. There was no Tinel's sign.
Electrodiagnostic testing showed evidence for a mild median nerve entrapment at the wrist on the right. Treatment with a resting wrist splint failed to adequately relieve the symptoms. Surgical carpal tunnel release was followed by marked improvement.
The etiology of carpal tunnel syndrome is compression of the median nerve in the carpal tunnel. The carpal bones form the floor and walls of the carpal tunnel, and the roof is created by the transverse carpal ligament. Nine flexor tendons with their sheaths accompany the median nerve in the carpal tunnel. Just before entering the carpal tunnel the median nerve gives off the palmar cutaneous branch that carries sensory fibers from the thenar eminence. After the median nerve exits from the carpal tunnel it gives off the thenar motor branch innervating the abductor pollicis brevis, the opponens pollicis, and the first and second lumbrical muscles. It sometimes also supplies the flexor pollicis brevis. The other branches are sensory digital branches that supply the thumb, index, middle finger, and the lateral half of the ring finger.
Carpal tunnel syndrome occurs in conditions that either reduce the space in the tunnel or cause increased susceptibility of the nerve.
Reduced space may be caused by tenosynovitis, rheumatoid arthritis, ganglia, osteophytes, osteosis, anomalous muscles, or tumors. Fluid retention is thought to be responsible in pregnancy, during lactation, or during the use of estrogens. Conditions with increased susceptibility of the nerve include diabetes, hypothyroidism, hereditary neuropathy with pressure palsies, acromegaly, and focal amyloid deposition that can be idiopathic or secondary to a genetic defect, systemic amyloidosis, or dialysis.
The prevalence of cardiac amyloidosis in patients who underwent carpal tunnel syndrome surgery was reported as 1.2% in 1 study. However, the prevalence was 5.5% in patients with left ventricular hypertrophy and 13.6% in patients with bilateral carpal tunnel syndrome. Patients with occupational risk factors were excluded in this analysis (62). One other study showed increased prevalence of amyloidosis, heart failure, and other cardiovascular outcomes in patients who underwent carpal tunnel syndrome surgery, compared to matched control subjects from general population (15).
Work-related carpal tunnel syndrome occurs with repetitive hand and wrist movement and is seen with a variety of activities and occupations. Increased pressure within the carpal tunnel due to certain positions of the hand and wrist and edema of the flexor tendons are thought to contribute to occupational carpal tunnel syndrome. Excessive computer use, particularly mouse usage, might be a minor risk factor for carpal tunnel syndrome compared to other occupational groups (51). In fact, a retrospective study looking at 100 patients with carpal tunnel syndrome showed predominance of elements that were unrelated to working at a computer. Carpal tunnel syndrome was also seen in people working physically and even among unemployed people (24).
Although the vast majority of carpal tunnel syndrome occurs sporadically, genetic factors may play a role. There is reportedly an autosomal dominant form of carpal tunnel syndrome (35). Rare, inherited connective tissue diseases such as mucopolysaccharidosis can cause severe carpal tunnel syndrome, and there is increasing literature looking at carpal tunnel syndrome and hereditary cardiac amyloidosis due to recent treatment availability for hereditary transthyretin amyloidosis. One single center study showed high prevalence of carpal tunnel syndrome in patients with hereditary transthyretin amyloidosis. The latency between carpal tunnel syndrome surgery and diagnosis of amyloidosis is long among patients with transthyretin amyloidosis. There was also a suggestion that carpal tunnel syndrome might be predictive for future occurrence of systemic (predominantly cardiac) ATTR amyloidosis (02); however, more studies may be necessary to establish this.
Acute carpal tunnel syndrome is mostly seen in the setting of traumatic injury to the hand or wrist and occasionally the forearm. It can be caused by the common Colles' fracture of the distal radius. Furthermore, bleeding into the carpal canal due to coagulation disorders seen with leukemia, hemophilia, or anticoagulant therapy can provoke acute carpal tunnel syndrome. Urgent surgical release is indicated for acute severe carpal tunnel syndrome.
Subacute carpal tunnel syndrome, with symptoms usually presenting within 1 week, may occur after rear- or front-end automobile collisions, presumably through hyperextension of the wrist against the steering wheel (12). Manifestations of carpal tunnel syndrome can also be seen in a much more delayed fashion after traumatic injury and have been described after a variety of fractures, lacerations, and burns.
The pathogenesis and pathophysiology of carpal tunnel syndrome is predominantly attributable to nerve dysfunction secondary to chronic mechanical compression. Histological abnormalities consist of paranodal myelin retraction with bulbous paranodal swellings, segmental demyelination, and variable degrees of axonal degeneration as well as remyelination and axonal regeneration. There is also a focal increase in endoneurial and perineurial connective tissue and thickening of the blood vessels. The contribution of superimposed ischemia in causing some of these connective tissue changes and axonal degeneration is not well defined.
The most detailed histological data are from studies in guinea pigs who spontaneously develop entrapment neuropathy in the feet when housed in wire cages (41) The findings correlate in general with the limited number of available autopsy studies in humans.
Nerves entrapped in the carpal tunnel are more likely than normal nerves to become symptomatic with ischemia (17). Muscle weakness and clinical sensory loss correlate with the severity of abnormalities on nerve conduction studies, whereas pain and paresthesias do not correlate with electrodiagnostic data. It is postulated that the paresthesias reflect spontaneous activity in the damaged nerve induced by ischemia.
Pressure measurements in the carpal tunnel with a wick catheter support the concept of increased pressure as a cause of carpal tunnel syndrome. Increased pressures of 30 mm Hg, which is just below the threshold for sensory symptoms, have been demonstrated in patients with carpal tunnel syndrome at rest. Wrist flexion and extension produce further increases and eventual neurologic dysfunction.
In a population study in Rochester, Minnesota (1976-1980) the prevalence was estimated at 125 per 100,000. The incidence of carpal tunnel syndrome was 0.12 per 1000 person-years with a peak at ages 55 to 64 and a female to male ratio of 2:8. In another study, in Sweden, 2.7% of a population of 170,000 had clinically and electrophysiologically confirmed carpal tunnel syndrome (01). In a Washington state workers study (1984-1988) the incidence was 1.7 per 1000 person-years with a peak at ages 25 to 34 and a female to male ratio of 1:2. Although the methodology in these studies is not identical, the findings support a correlation between manual work and carpal tunnel syndrome. A study looking at a job exposure matrix of 3452 active workers from a public data source of several industries showed that workers with high force/high repetition jobs had the highest prevalence of carpal tunnel syndrome (odds ratio=2.14-2.95) (11). In general, high rates of carpal tunnel syndrome are associated with activities where repetitive hand movements are frequent.
Ergonomic intervention may be helpful in preventing carpal tunnel syndrome by focusing on tool design, improvement of workstations, the avoidance of repetitive pinching, wringing, and grasping motions as well as other measures.
Carpal tunnel syndrome should be differentiated from other neurologic disorders that can cause pain, numbness, tingling, and weakness in the hand such as cervical radiculopathy, polyneuropathy, other entrapments of the median nerve, ulnar neuropathy, and brachial plexopathy. Non-neurologic causes of wrist and hand pain include de Quervain tenosynovitis of the abductor pollicis longus and extensor pollicis brevis tendons, trigger finger, nonspecific tenosynovitis, osteoarthritis of the basal joints of the thumb, and Raynaud disease.
A thorough clinical examination in combination with electrodiagnostic testing usually leads to the correct diagnosis. Occasionally, radiological investigation is necessary, especially when cervical radiculopathy is suspected.
The combination of carpal tunnel syndrome with a more proximal cervical nerve root compression has led to the concept of the "double crush syndrome" (57). However, there is no convincing scientific evidence for additional vulnerability to carpal tunnel syndrome on the basis of proximal axon damage from a cervical radiculopathy (60).
Electrodiagnostic testing has an important role in the diagnostic workup for carpal tunnel syndrome. It can document a median nerve entrapment at the wrist and thereby support the diagnosis of carpal tunnel syndrome in the presence of appropriate symptoms. Simpson was the first to describe the increased distal motor latency of the median nerve stimulated at the wrist (52). Since then, increasingly refined nerve conduction techniques have been developed to demonstrate slowing of conduction in the median nerve across the carpal tunnel.
Electrodiagnostic testing usually includes motor and sensory nerve conduction studies of both median nerves and at least 1 ulnar nerve. Needle examination of the abductor pollicis brevis muscles is routinely performed to look for denervation. Needle examination of several other upper extremity muscles and the cervical paraspinal muscles is often necessary to evaluate for other entrapment neuropathies, plexopathy, or radiculopathy.
Sensory nerve conduction studies are the most sensitive in confirming the diagnosis. The most common finding is an increase in distal latency due to focal slowing of conduction across the carpal tunnel. Special adaptations may be necessary to demonstrate mild carpal tunnel syndrome, these include (20):
The next most sensitive feature is a decrease in amplitude of the sensory response. Increased distal motor latency is seen less frequently and reduced amplitude of the median motor response is even less common. In more severe carpal tunnel syndrome there is acute or chronic denervation on needle examination of the abductor pollicis brevis, suggesting axon loss of median motor nerve axons. One study pointed out that the comparison of the median-second lumbrical distal latency and ulnar interossei/third lumbrical distal latency showed high sensitivity and specificity (28). The second lumbrical-interosseous distal motor latency comparison test proved to be a valuable electrodiagnostic technique for carpal tunnel syndrome diagnosis, even in the most severe patients (30). The severity of clinical weakness and sensory loss, but not of the complaints of tingling and pain, correspond in general with the severity of electrodiagnostic findings.
Median and sensory nerve conduction studies provide accurate and reproducible measurements that can confirm a clinical diagnosis of carpal tunnel syndrome with a high degree of sensitivity (66% to 82%) and specificity (82% to 97%) (21).
However, studies have suggested that ultrasound and clinical diagnostic tools such as carpal tunnel syndrome 6 (CTS 6) are highly accurate in the diagnosis of carpal tunnel syndrome and that nerve conduction studies are not necessary in most cases (16).
MRI of the wrist can document abnormalities in the median nerve that are compatible with carpal tunnel syndrome (05; 22). MRI may be helpful if tumors or other structural abnormalities are suspected or after surgery has failed. A routine wrist x-ray is not useful (04).
Ultrasound is another useful tool for assessment of carpal tunnel syndrome. Various measurements, including the wrist-to-forearm median nerve area ratio (WFR) and the cross-sectional area of median nerve at the wrist (CSA-W), have been shown to have high correlation with severity grade of carpal tunnel syndrome. WFR has been shown to be superior to CSA-W for diagnosis and grading of severity of carpal tunnel syndrome (23). The pisiform CSA measurements are more reliable for diagnosing early stages of carpal tunnel syndrome. CSA (pisiform)/CSA (ulnar) have lower diagnostic value for diagnosing carpal tunnel syndrome (61). An evidence-based guideline was also published for use of ultrasound in the diagnosis of carpal tunnel syndrome. Ultrasound measurement of median nerve cross-sectional area has been found to be accurate and may be offered as a diagnostic test for carpal tunnel syndrome. The guideline also showed that ultrasound probably adds value to electrodiagnostic studies when diagnosing carpal tunnel syndrome and should be considered in screening for structural abnormalities at the wrist in those with carpal tunnel syndrome (07). In addition to diagnosis, ultrasonography may be valuable in staging carpal tunnel syndrome, especially by combining multiple measures. In a study of 104 participants, an 8-point scoring scale, including patient-reported symptoms, functional deficits, provocative testing, nerve cross sectional area, and nerve longitudinal appearance, classified severity accurately for 79.8% of participants (48). One study showed that the CSA of the median nerve in the area immediately proximal to the carpal tunnel inlet is the most sensitive method to diagnose the early stage carpal tunnel syndrome (03).
Carpal tunnel syndrome, unless accompanied by a severe clinical deficit, is usually first treated conservatively with the use of a resting wrist splint and advice to reduce provoking activities. Orthosis use at night for 6 weeks in patients with mild to moderate carpal tunnel syndrome was associated with positive electrophysiological effects (09). This is successful in about 50% of patients but gives permanent relief only in 50% of responders. Extracorporeal shock wave therapy and ultrasound therapy showed some improvements in pain and function (43; 58). A metaanalysis of randomized trials on the effectiveness of low-level laser therapy on carpal tunnel syndrome revealed that low-level laser improved hand drip, visual analog scale, and sensory nerve action potential after 3 months of follow-up in mild to moderate carpal tunnel syndrome (32). Steroid injections into the carpal tunnel can provide immediate relief but this is usually not sustained and local complications may occur. However, studies showed effectiveness of ultrasound-guided carpal tunnel injection using in-plane ulnar approach to be more effective than out-plane or blind injection (29). If conservative treatment is not effective, surgical carpal tunnel release is performed. Surgical treatment relieves symptoms significantly better than splinting (59). This results in an improvement rate of 80% to 90% (13). Patients can usually return to work in 2 to 3 weeks. The success rate is slightly lower in workers' compensation patients with a return to work after a longer period. Elderly (older than 70 years) patients have more severe clinical and electrophysiological findings preoperatively but do show high satisfaction scores after surgery (37; 56). Outcome after carpal tunnel surgery in patients with diabetes is similar to that of nondiabetic patients (55). One survey looking at the practice patterns of management from 1987 to 2011 showed increasing use of splints and corticosteroid injections, treating nonoperatively longer, and narrowed surgical indications (31). Orthotic use and duration postoperatively decreased significantly. Endoscopic carpal tunnel release (ECRT) supposedly produces less scarring than open release but is more expensive and precludes visualization of the median nerve proper. Controversy remains about which procedure is the best (14; 38; 19; 39; 53; 50; 54). A 5-year ECRT prospective nonrandomized clinical trial of 176 patients with carpal tunnel syndrome showed proximally present wrist crease as the optimal site to make the skin incision and also established signs to look for in a completely divided retinaculum (40). Other novel procedures have been described for treatment, including sonographically guided percutaneous needle release of the carpal tunnel (34) and ultraminimally invasive ultrasound-guided carpal tunnel release (47). Collagen nerve wrapping has been shown to inhibit nerve tissue adhesions and diminish inflammatory and immunologic reactions in nerve surgery (26). Failure of carpal tunnel surgery is reported in about 5% to 10% of surgeries. Incomplete sectioning of the transverse carpal ligament, scar formation, and hand symptoms due to other causes are some of the reasons.
The prognosis for recovery is good with either conservative or surgical treatment. There is a significant improvement of clinical and subjective outcomes after carpal tunnel syndrome surgery, which is independent of sociodemographic and clinical characteristics (10). Patients with severe carpal tunnel syndrome should be informed that recovery may be more prolonged after surgery, and numbness may continue (27). The complications include persistent weakness and sensory loss in the distal median nerve distribution. The most dramatic complication is complex regional pain syndrome, a condition that is characterized by severe pain, hyperalgesia, dysesthesia, and trophic disturbances.
During pregnancy there is an increased incidence of carpal tunnel syndrome, presumably on the basis of fluid retention. Treatment is usually with conservative measures because spontaneous recovery occurs after delivery in about 50% of patients (44). If symptoms persist, steroid injection or surgical carpal tunnel release should be considered.
Mamatha Pasnoor MD
Dr. Pasnoor of the University of Kansas Medical Center received an honorarium from Argenx BVBA as a consultant and medical advisor.See Profile
Randolph W Evans MD
Dr. Evans of Baylor College of Medicine received honorariums from Abbvie, Amgen, Biohaven, Impel, Lilly, and Teva for speaking engagements.See Profile
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