Many types of tumors may present with symptoms that appear to be CTS. The most proximal site of compression was described by Dunkow et al. in 2004, when they reported on a glioblastoma causing symptoms of numbness and tingling in the median nerve distribution [6]. The patient presented with numbness in the left index, middle, and ring fingers and a positive Tinel’s over the median nerve at the wrist, but a negative Phalen’s test . Electrodiagnostic studies suggested cervical pathology; however, a cervical spine magnetic resonance (MR) scan excluded a cervical etiology. Symptoms progressed to involve the small finger, and the patient had decompression of median and ulnar nerves at the wrist with no improvement. Following development of wrist extensor weakness, MR of the brain showed a 5 cm parietal lobe tumor. This case highlights the importance of asking about central symptoms such as headaches, personality changes, nausea/vomiting, seizures, or memory loss.

Cervical spine neoplasms have also been implicated in creating carpal tunnel complaints. Tumors of the foramen magnum can present with hand numbness, weakness, and clumsiness before other neurologic findings are obvious. In a series of 57 patients, Yasuoka et al. found three patients were initially misdiagnosed with carpal tunnel syndrome [7]. These patients will often have other findings not typical of carpal tunnel syndrome including gait disturbances, hyperreflexia, neck pain, and a Babinski sign [8].

Tumors in the upper apices of the lungs, such as a Pancoast tumor , may encroach on the brachial plexus as the tumor becomes larger [9]. As the tumor escapes the confines of the thoracic cavity, it invades the superior thoracic inlet and can compress the medial cord of the brachial plexus [10]. Sensory and motor deficits typically also involve the ulnar nerve distribution. Additionally, Horner’s syndrome is present in up to 50% of patients, and many will also have constitutional symptoms such as fatigue, fever, or weight loss. Interestingly, pulmonary symptoms are uncommon early in the disease process.

Peripheral nerve tumors such as a schwannoma can develop within the median nerve or its branches and cause carpal tunnel symptoms [11–13]. Although these are usually asymptomatic at first, as they enlarge, neurologic symptoms may develop. Schwannomas are most often benign, slow-growing, encapsulated lesions that are amenable to surgical excision. Unlike neurofibromas , schwannomas can be separated from the nerve avoiding injury to surrounding axons. In addition to symptoms of numbness/tingling, a palpable mass may be present as it enlarges. Padua et al. described five patients found to have schwannomas with presenting symptoms of carpal tunnel syndrome, three of whom had prior surgical treatment with persistent symptoms. They found ultrasound to be particularly helpful in these cases which tended to have some “incongruous aspects” [13]. Additionally, when a peripheral nerve tumor is suspected, MRI should be obtained to evaluate the characteristics of the mass prior to consideration of surgical excision or biopsy, as malignancy may be present.

Neuropathy is a broad category with many conditions that cause median nerve symptoms. Patients often have trouble deciphering which digits have sensory abnormalities and may misinterpret radial or ulnar neuropathy as carpal tunnel syndrome. Pronator syndrome is a compressive neuropathy involving the median nerve occurring at the elbow. Patients have numbness in the median nerve distribution as with carpal tunnel syndrome with the addition of numbness in the territory of the palmar cutaneous branch of the median nerve. Complaints of pain and numbness are more common during activity with absence of nocturnal symptoms. Provocative tests include tenderness along the course of the median nerve across the elbow, pain with resisted pronation with the elbow in extension, and pain with resisted middle finger proximal interphalangeal joint flexion. Pronator syndrome is rare in comparison to CTS, but may coexist and should be considered in all patients presenting with carpal tunnel complaints [14].

Peripheral neuropathies have many potential causes including diabetes, nutritional deficiencies, human immunodeficiency virus, uremia, and vascular. Many cases are symmetric with symptoms commonly affecting the distal aspect of the longest nerve fibers, explaining typical onset of foot symptoms prior to those in the hand. Polyneuropathy may present with asymmetric symptoms though, especially in diabetics [15]. In these cases, it can be more difficult to differentiate from a compressive etiology. Diagnosis of peripheral neuropathy is based on a combination of neuropathic symptoms, signs, and electrodiagnostic studies, with signs being better than symptoms in making the diagnosis [16]. Signs of sensory loss occur in non-dermatomal, non-single nerve distribution patterns. Motor findings are atrophy and weakness of intrinsic muscles, with secondary joint deformity. Tendon reflexes are often diminished or absent. The electrodiagnostic study most helpful for confirming the diagnosis of a peripheral neuropathy is the nerve conduction study (NCS) . Findings of an abnormality of any attribute of nerve conduction in two separate nerves, one of which must be the sural nerve, are the minimum criterion to support the diagnosis. If sural sensory and peroneal motor NCSs are normal, there is no evidence of a peripheral neuropathy [16]. If either is abnormal, NCS of at least the ulnar sensory, medial sensory, and ulnar motor nerves in both arms is performed. The addition of radial nerve studies is helpful particularly in those patients with suspected carpal or cubital tunnel syndrome, since compressive neuropathy may coexist with peripheral neuropathy.

Multiple sclerosis is an uncommon cause of failed carpal tunnel decompression [17]. Presenting symptoms are commonly central, such as unilateral visual disturbance, hemifacial spasm, and vertigo [18]. Lhermitte’s symptom , an electric-shock-like sensation that can run down the back, or into the arms and/or legs triggered by neck motion, is strongly linked to multiple sclerosis [19]. Other peripheral symptoms may occur, which may simulate carpal tunnel syndrome; however, patients do not have typical nocturnal or provocative daytime symptoms.

Lesions of the brachial plexus may also create symptoms that may be confused with carpal tunnel syndrome. The median nerve originates from the lateral and medial cords of the brachial plexus with contributions from C6 to T1. Traumatic causes of brachial plexopathy are typically high-energy and result from motorcycle or other motor vehicle accidents where the arm is subjected to a traction or crush injury. Patients with anterior shoulder dislocation may also have compressive injury to the plexus. “Burners” or “stingers” are traction injuries occurring when the head and neck are forcefully pushed sideways and down, affecting one arm. They occur during a fall to the head, as may occur during wrestling or most commonly during a football tackle. These traumatic causes are usually easily differentiated from CTS due to the history of injury, though in multi-trauma patients, injury to the shoulder and hand/wrist may coexist, and acute CTS should be excluded by clinical exam and/or pressure monitoring of the carpal tunnel.

Neuralgic amyotrophy , or Parsonage-Turner syndrome , is a rare, likely autoimmune, disorder which causes pain and sensory and motor changes in peripheral nerves. Pain is the presenting symptom in 90% of cases, followed by weakness within 24 h in one third of patients, within 2 weeks in 70% of patients, and within 1 month in 85% [20]. Most commonly, the shoulder girdle muscles are involved, including the infraspinatus, supraspinatus, deltoid, biceps, and triceps, though weakness may be limited to the muscles supplied by a single nerve. Paresthesias and hypoesthesia are present in the majority of patients, again most frequently about the shoulder. Pure sensory neuralgic amyotrophy can occur, and when it does, it typically affects the median, medial antebrachial, and lateral antebrachial cutaneous nerves, potentially mimicking carpal tunnel syndrome. The abrupt onset of the symptoms, significant pain, and weakness in muscles other than the thenars help distinguish patients with Parsonage-Turner syndrome from those with carpal tunnel.

Neck pain is a common condition, with 1 year prevalence rates of 4.8–79.5% (mean 25.8%) [21]. Underlying spondylosis , spondylolisthesis , and disc herniation may lead to nerve compression and symptoms of a peripheral compressive neuropathy. Cervical radiculopathy involves one or more nerve roots, creating pain, numbness, and weakness in a dermatomal distribution. Sixth cervical root compression, seen in 25% of patients, causes numbness in the thumb and index fingers, whereas seventh cervical root involvement (60% of patients) causes numbness in the middle finger [22]. Patients with C6 involvement most closely mimic carpal tunnel syndrome, but these patients do not typically exhibit abductor pollicis brevis atrophy as is seen in advanced carpal tunnel. Nocturnal symptoms are less frequent as well. In a study by Chow et al., 84% of patients with isolated carpal tunnel syndrome had nocturnal symptoms compared to only 10% in the group with isolated cervical spondylosis [23]. Additional findings in patients with C6 radiculopathy include weakness (elbow flexion, wrist extension, and forearm supination), diminished reflexes (brachioradialis and biceps), and cervical pain, loss of motion, and a positive Spurling’s test (reproduction of symptoms by positioning the neck in extension, rotating toward the side of symptoms, and applying axial load).

Cervical myelopathy occurs secondary to spinal cord compression. It may result from disc herniation, spondylolisthesis, or a space-occupying lesion. The clinical picture in patients with myelopathy tends to be quite variable and requires a high index of suspicion. Crandall and Batzdorf described five broad categories of cervical myelopathy including “brachialgia and cord syndrome” which may present with symptoms of carpal tunnel syndrome [24]. Symptoms may be non-dermatomal and often bilateral. Patients complain of diffuse numbness and the insidious onset of clumsiness, hand weakness, and worsened handwriting. As the condition advances, intrinsic atrophy progresses and may become severe. This constellation of findings was described as “myelopathy hand” by Ono et al. in 1987 [25]. They described two signs specific to the disorder. The “finger escape sign” is positive when after asking the patient to extend and adduct their fingers, the small finger drifts into abduction in less than 30 s. The “grip and release” test indicates myelopathy when the patient is unable to repeatedly open and close their fists at least 20 times in 10 s [22]. Myelopathic patients have weakness and spasticity, with exaggerated wrist flexion during finger extension and wrist extension during finger flexion.

Ziadeh and Richardson described the case of a patient with cervical syrinx who presented with symptoms of carpal tunnel syndrome [26]. The patient presented with a several year history of left thumb, index, and middle finger numbness. Symptoms were worse at night and with keyboard use. A night splint failed to control symptoms, as did physical therapy, ergonomic evaluation, and prescription anti-inflammatory medication. The patient denied weakness, clumsiness, or gait disturbance, but close physical evaluation demonstrated hyperreflexia and a positive Spurling’s maneuver, highlighting the importance of a complete examination in all patients with presumptive diagnosis of carpal tunnel syndrome. A cervical spine MR demonstrated a syrinx from C1–C2 to T10–T11 with an Arnold-Chiari type I malformation .

Inflammatory disease can not only be a cause of carpal tunnel syndrome but can also mimic carpal tunnel by creating neuropathy proximally. Disorders such as polyarteritis nodosa, lupus, and rheumatoid arthritis can develop vasculitis affecting the peripheral nerves and lead to upper extremity dysesthesia. A case highlighting this etiology was presented by Sethi et al. in a patient with Churg-Strauss syndrome [27]. Churg-Strauss syndrome is an autoimmune condition causing asthma and inflammation of small- and medium-sized vessels leading to mononeuritis multiplex or polyneuropathy. In their case, the patient presented with right thumb, index, and middle finger numbness. Neurologic symptoms progressed with involvement of the contralateral hand and visual disturbance leading to consideration of alternative diagnoses.

Polymyalgia rheumatica can also cause symptoms of carpal tunnel syndrome. In a series of 177 patients, Salvarani et al. found 14% with carpal tunnel complaints [28]. Patients with polymyalgia rheumatica often have multiple distal musculoskeletal findings including edema, tenosynovitis , and joint pain which can help differentiate the disease from idiopathic carpal tunnel syndrome. Patients are usually over the age of 50 and have an elevated erythrocyte sedimentation rate and C-reactive protein. Response to oral corticosteroids is dramatic, while nonsteroidal anti-inflammatories are ineffective.

Traumatic injuries to the median nerve must always be considered when evaluating a patient with symptoms of carpal tunnel syndrome. Sharp lacerations from a piece of glass or a knife may be obvious. Less obvious situations may present with dysesthesias and a remote history of injury. Browett et al. reported on two patients who suffered injuries to their volar wrists from a piece of glass with no immediate neurologic symptoms [29]. One patient developed paresthesia in the median nerve distribution 3 days later, while symptoms took 3 months to occur in the other when while extending her wrist, the patient had the sudden onset of pain and numbness in her thumb. Findings at exploration in the latter patient confirmed partial laceration of the median nerve with a glass fragment embedded in the radial side.

Blunt trauma occurring anywhere in the extremity or neck can injure nerve fibers which terminate in the median nerve or the median nerve itself. As these are typically associated with a significant trauma, the location of the injury is often known. However, acute carpal tunnel can coexist in patients with concomitant injury to the hand or wrist or develop from reperfusion injury. A detailed neurologic examination is critical in trauma patients to determine whether nerve damage is present as a result of the injury. In obtunded patients in which an examination isn’t possible, close compartment monitoring is necessary, and prophylactic fasciotomies and carpal tunnel decompression are warranted in patients with prolonged arm ischemia due to vascular injury.

Symptoms of carpal tunnel syndrome may occur with a number of vascular conditions. Raynaud’s disease , hypothenar hammer syndrome , and hand-arm vibration syndrome can all cause symptoms of numbness and tingling in the median nerve distribution [9, 30, 31]. In Raynaud’s disease , patients complain of blanching or cyanosis in the fingers triggered by cold or other stressors. Numbness can coexist with the vascular changes and may be the primary complaint. Patients with carpal tunnel syndrome may also complain of coldness in the fingers which is thought to be caused by increased sympathetic activity during periods of increased median nerve compression. Treatment should be focused based on which factors most frequently trigger the symptoms, concentrating on Raynaud’s for those with symptoms only occurring with cold exposure. Patients may also suffer from both conditions. In a group of 30 patients with carpal tunnel syndrome, Chung et al. [32] found 60% had concurrent Raynaud’s disease based on objective impairment of arterial pulse following cold immersion.

Hand-arm vibration syndrome is characterized by neural and/or vascular symptoms in patients with a history of vibration exposure. Neural symptoms are due to damage to the nerves resulting in paresthesias, pain, sensory loss, and muscle wasting. Finger blanching and pain result from digital vessel spasm and progressive occlusion. Some patients will progress to trophic changes in the fingertips as is seen in other causes of vascular ischemia. Diagnosis is based on the presence of symptoms with a history of significant vibration exposure and should be considered in patients with a 5-year vibration exposure over 5000 h [31]. The importance of distinguishing between the two conditions was highlighted by Pelmear et al. who found that surgical treatment may make the hand-arm vibration syndrome patient worse due to further reduction in grip strength [33].