Carpal Tunnel Syndrome
Autoimmune Neuropathies
Ulnar Neuropathy
Meralgia Paresthetica

Carpal Tunnel Syndrome


Carpal tunnel syndrome (CTS) is the most frequently encountered mononeuropathy in the clinical practice. Although now a well recognized entity, it took almost 100 years from the initial observations until the pathophysiology of the disorder was finally accepted as a median nerve compression at the wrist. Sir James Paget (1854) was the first to describe the clinical features of CTS.

A landmark article of Marie and Foix (1913) provided the first comprehensive clinical and pathologic assessment of a non-traumatic median nerve lesion at the wrist. Despite these correct observations of Marie and Foix, the clinical symptoms we now understand to represent CTS were generally judged secondary to proximal nerve compression. The most common treatment option in first four decades of the century was a cervical rib excision. Influential physicians such as F.

Buzzard (1907), S.A. Kinnier Wilson (1913) and P. Sargent (1921) popularized this approach, concluding that a cervical rib, in patients with aberrant innervation of the opponens pollicis and abductor pollicis brevis by the seventh cervical root, could compress the C7 root and produce thenar atrophy and sensory changes in the first three fingers. It was the clinical failure of the cervical rib resections that led to a fundamental reconsideration of the pathophysiology of the disorder.

In the 1950's, G. Phalen published a series of landmark articles solidifying and further defining CTS as a clinical syndrome resulting from median nerve compression at the wrist. He confirmed the usefulness of Tinel’s sign as the quintessential maneuver to provoke sensory phenomena in CTS. Finally, he concluded that transection of the carpal ligament could decompress the nerve sufficiently to restore its normal function.

It took more than 4 decades from the initial recognition that CTS was caused by median nerve compression at the wrist until transection of the transverse carpal ligament become the main therapeutic option for CTS.

Simovic & Weinberg

Archives of Neurology,

Case report:

A 58 y.o. mechanic presents with a severe wrist pain and tingling in his fingers with sparing of the 5th finger. His nocturnal symptoms are very prominent and shaking of the hands is decreasing symptoms. Some neck discomfort and stiffness have been present for several years with occasional radiation to the arms.

Physical examination showed weakness of the bilateral APB muscles and a decreased sensation in the thumb, index and middle fingers. Percussion of the median nerve at the wrists provoked tingling in the index and middle fingers (Tinel’s sign).

What does the clinical picture suggest and what differential diagnosis must be considered?

Carpal Tunnel Syndrome is the most likely diagnosis. Alternative options would be proximal median nerve lesion ( Pronator Teres Syndrome or ligament of Struthers compression) or a C6 root affliction.

How may an EMG help?

The role of the EMG is to evaluate for presence and severity of CTS, rule out proximal median nerve lesion, evaluate for a cervical radiculopathy and screen for a diffuse condition such as polyneuropathy.

What did the EMG show?

It showed bilaterally prolonged medial motor distal latency with a decreased bilateral median sensory amplitude and a prolonged median sensory and mixed nerve peak latency. All other nerve conduction studies were normal. EMG showed abnormal recruitment pattern in bilateral APB muscles and no evidence of active or chronic neurogenic changes in bilateral Deltoid, Biceps, Triceps, Pronator Teres and FDI muscles.

Which conditions could be associated with CTS?

Diabetes mellitus, rheumatoid arthritis, gout, amyloidosis, myxedema, multiple myeloma, pregnancy, hemodialysis, SLE, sceroderma, acromegaly, repetitive wrist motion stress injury, hypothyroidism, ganglion, sarcoid , and previous radius fracture. Most cases are idiopathic.

What are the therapeutic options?

Depending on the clinical and electrophysiologic severity, conservative options (splinting, anti-inflammatory medications or wrist steroid injections) may be tried first. If no improvement is seen, a surgical approach (open or endoscopic) may be necessary. Surgical CT release was shown to have a high success rate.

CTS Quantitative Screening Scale

Simovic D & Weinberg D.: A quantitative clinical scale for the carpal tunnel syndrome; Neurology, 50 (4): A302

Quantitative CTS Screening Scale was developed in order to assist in screening patients with a potential CTS. The positive predictive value (PPV) for the total score was 79.2% with negative predictive value (NPV) of 91.7%. Using a discriminant function analysis the best linear function for predicting the CTS was: 6.8 + 4.7* median sensory loss + 3.95* hand posture change symptom amelioration + 3.8* sleep symptoms + 2.6* thenar weakness + 2.6* Tinel’s/Phalen’s sign + 2.5* repetitive motion symptom aggravation. The new linear function score correlates well with the total scale points (P < 0.001; r = 0.79) with a PPV = 91.7% and a NPV= 98.2%.

Clinical diagnostic parameters:


1) pain in the hand, forearm or upper arm 


2) paresthesias or numbness in the hand


3) weakness or clumsiness in the hand


4) occurrence of the above symptoms isolated    to median nerve distribution


5) symptoms provoked by sleep


6) symptoms provoked by sustained hand/arm  position or repetitive action of the hand and wrist


7) symptoms decreased with a change in hand position


8) symptoms decreased with hand shaking


9) presence of Tinel’s or Phalen’s sign


10) sensory loss in the median nerve distribution


11) weakness or atrophy of thenar muscles




CTSscale grade: Total score
Unlikely-CTS 1-6
Possible-CTS 7-8
Probable-CTS 9-30

Autoimmune Neuropathies

The exact prevalence of neuropathies in the general population is unknown. The Neuropathy Association, New York, USA, estimates that in the United States alone, up to 20 million patients suffer from peripheral neuropathies. Polyneuropathies have a variety of causes including a subset mediated by immune mechanisms

Guillain-Barré syndrome and variants

Guillain-Barré syndrome (GBS) has an annual incidence of 1 – 2 cases per 100,000 in the general population. Its variants include two subgroups. The first, consisting of syndromes with predominant weakness, includes acute inflammatory demyelinating polyradiculoneuropathy (AIDP), acute motor axonal neuropathy (AMAN) and acute motor sensory axonal neuropathy (AMSAN). The second subgroup, where weakness is not predominant, includes Miller Fisher syndrome, acute panautonomic neuropathy and pure sensory neuropathy.

In GBS syndromes with predominant weakness, the clinical syndrome usually follows a viral illness (60-70%) or Campylobacter jejuni enteritis (30-40%). Clinical presentation usually begins with paresthesias and lower back pain. Ascending muscle weakness follows. The disease can progress for days up to four weeks. Autonomic manifestation, partial or complete ophthalmoplegia and facial weakness may be seen. Ventilator support may be needed in a third of patients. In addition to muscle weakness, physical examination shows distal sensory loss, except in AMAN form, and absent or depressed muscle stretch reflexes. Patients may develop ataxia, tremor, and dysautonomia. Examination of cerebrospinal fluid (CSF) shows elevated protein without leukocytosis in 90 percent of patients.

Electrophysiologic features are characterized by prolonged distal and F-wave latencies, demyelinating ranges of conduction velocities, and partial motor conduction blocks. Although sensory studies are normal in AMAN, in both AMSAN and AMAN a marked reduction of compound muscle action potential amplitude is prominent.

Chronic inflammatory demyelinating polyneuropathy

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired immune mediated neuropathy with a peak incidence in the 40 - 60 year age group. The prevalence is estimated from 1 – 7.7 per 100,000 population and rises with age. It is clinically characterized by a slowly progressive symmetric weakness and a panmodal sensory loss. Weakness usually affects the legs first and is not associated with atrophy or fasciculations. A large fiber sensory loss is present with absent or depressed stretch reflexes. By definition, symptoms develop over at least two months. Elevated CSF proteins are seen in 95 percent of CIDP patients.

The electrophysiologic features include reduction in conduction velocity in two or more nerves, partial conduction block , prolonged distal latencies in two or more motor nerves and absent F-waves or prolonged minimum F-wave latencies. Several variants of CIDP have been described. The main variant with asymmetric findings is referred to as a multifocal acquired demyelinating sensory and motor (MADSAM) neuropathy. It often begins in one limb followed by a spread to other limbs in an asymmetric fashion. Further variants include distal acquired demyelinating sensory (DADS) neuropathy and multifocal acquired sensory and motor (MASAM).

Multifocal motor neuropathy

Multifocal motor neuropathy (MMN) is a rare disorder with a prevalence of 1 – 2 per 100,000. This unique neuropathy is characterized by a progressive, asymmetric, distal weakness that frequently presents as a wrist drop, a bicep weakness or a foot drop with minimal or absent sensory symptoms. Weakness progresses insidiously or in a stepwise manner. Muscle cramps and fasciculations are frequently seen coupled with asymmetric stretch reflexes. Electrophysiologic findings show a persistent, focal, motor conduction block outside the common compression sites. Prolonged F-wave latencies and reduced motor conduction velocities are also seen, with normal sensory responses. Laboratory investigations may be helpful in establishing diagnosis as antibodies to GM-1 are elevated in 40-50% of patients. Antibodies to other glycolipids, including asialo-GM1, GD1a and GM2, may be seen in a small percentage of patients. Examination of CSF in patients with MMN is usually normal.

Monoclonal gammopathy of undetermined significance and neuropathy

Paraprotein associated neuropathies are a clinically heterogeneous group, depending on the type of a monoclonal paraprotein. Most of the affected patients do not have an underlying plasma cell disorder, thus the term monoclonal gammopathy of undetermined significance (MGUS) was coined. Commonly, patients are over the age of 50, with men being more affected than women. The course is slowly progressive for most of the patients, although rapid progression may be seen in a small number of cases. Approximately 55 percent of MGUS neuropathy patients have IgM monoclonal proteins, while 35 percent have IgG and 10 percent have IgA. In a subset of patients with IgM gammopathy and neuropathy, approximately 50% have antibodies to a myelin associated glycoprotein (MAG). The initial presentation of patients with anti-MAG antibodies is characterized by a mild, distal, lower extremity sensory disturbance. While approximately one-third of these patients have only sensory symptoms, most patients have some degree of distal weakness and in 20% the weakness is severe. Electrophysiologic studies of patients with an anti-MAG neuropathy are characterized by predominantly demyelinating features. Examination of CSF in patients with MGUS neuropathy may show normal or elevated proteins.

Treatment with IVIg

IVIg is a solution of a highly purified immunoglobulin, derived from a large pool of human plasma. The commercially available IVIg contains more then 95% of IgG and less then 2.5% of IgA.

The therapeutic dose of IVIg is 400 mg/kg/day, repeated over five days, for a total of 2gr/kg. The recommended rate of infusion should not exceed 200 ml/hr. Tolerability of IVIg is very good and adverse reactions are usually minor. The most common side effects are headache, nausea, chills, flushing, myalgia, hypotension, hypertension, chest discomfort, and fatigue. Infrequent adverse reactions include thromboembolic evens, skin reactions, aseptic meningitis, renal tubular necrosis, and severe anaphylactic reaction.


  • The therapeutic dose of IVIg, a highly purified immunoglobulin derived from human plasma, is 400mg/kg/day repeated over 5 days. Tolerability of IVIg is very good and adverse reactions are usually minor.
  • The benefits of IVIg therapy have been recognized through controlled studies for Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN). In monoclonal gammopathy of undetermined significance (MGUS) and neuropathy, the effectiveness of IVIg is variable.
  • Further controlled trials are needed to clarify the open questions in the treatment of autoimmune neuropathies, including the efficacy of a second IVIg infusion in non responders in GBS, maintenance IVIg dose and frequency in CIDP and MMN, efficacy of IVIg in diabetes associated CIDP and the benefit of combination therapy with other immunomodulating medications.