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Carpal tunnel syndrome is one of the most common conditions encountered in general neurological practice, the usual cause being occupational activities using repeated wrist movement such as housework, typing or gardening. Under normal conditions, the carpal tunnel is already crowded with structures including nerves and tendons, with little extra space to accommodate expansion of its contents. Any increase in volume may have a significant impact on its clinically most sensitive structure, the median nerve.1 In most cases, symptoms arise simply from excessive use of the hand producing friction and swelling of the nerve. Additional pathological conditions affecting the carpal tunnel include diabetes mellitus, pregnancy, tumours, myeloma, myxoedema, acromegaly and pathological enlargement of joints or tendons such as in rheumatoid arthritis.2 3 However, we have recently encountered an unusual cause for this otherwise common clinical condition, which clinicians should be aware of during normal clinical practice.
Tingling in the hands at night is most commonly related to carpal tunnel syndrome, one of the most common conditions encountered in general neurological practice. The carpal tunnel is already crowded with structures including nerves and tendons, with little extra space. Any increase in the volume of its contents may have a significant effect on the median nerve. Most cases of carpal tunnel syndrome are idiopathic, although known causes include diabetes mellitus, pregnancy, tumours, myeloma, myxoedema, acromegaly and pathological enlargement of joints or tendons such as in rheumatoid arthritis. We have recently encountered another unusual cause.
A 50-year-old man presented with a 3-month history of paraesthesia of the lateral three fingers of the right (dominant) hand. These symptoms kept him awake from sleep and worsened on the use of his right hand, restricting the use of his computer. In addition, he had generalised aches and pains including pain in the right shoulder. He also reported generalised fatigue and some weight loss for several months. He did not smoke, occasionally drank alcohol and had no significant medical history.
General physical examination was normal. He had mild muscle wasting in the arms and bilateral weakness (MRC grade 4/5), especially in the shoulder girdles and forearms, and absent deep tendon reflexes. Tinel's sign was positive on the right hand. In his legs, the power was normal and ankle reflexes were preserved, but knee reflexes were absent due to prior surgery. Plantar responses were absent and sensation was normal.
Nerve conduction studies showed a mild axonal peripheral polyneuropathy with absent right median nerve sensory nerve action potential at the wrist. Electromyography showed generalised fibrillation potentials and positive sharp waves associated with fasciculation potentials and myokymic discharges. Serum creatine kinase was elevated at 470 U/l (24–195).
Left deltoid muscle biopsy showed a few scattered atrophic fibres, but otherwise normal muscle morphology. There was extensive amorphous eosinophilic mural thickening of small arteries, within the epimysial and perimysial compartments (figure 1). Congo red staining (figure 2) confirmed this mural infiltrate to be vascular amyloid. There was no amyloid deposition within the endomysium or, apart from in the involved small arteries, the perimysium. The Congo red stain showed classic apple-green birefringence with polarised light (figure 3).
Echocardiography found a mildly thickened left ventricular wall, increased left ventricular filling pressure and dilated atria. Cerebrospinal fluid was acellular with a mildly raised protein at 0.52 g/l (0.15–0.45), but no oligoclonal bands were present.
We referred the patient to the National Amyloidosis Centre at the Royal Free Hospital, London. Additional physical findings from the Centre included macroglossia, hepatomegaly and a protodiastolic gallop murmur over the mitral valve.
Additional investigation findings included serum N-terminal pro-brain natriuretic peptide 78 pmol/l with normal serum cardiac troponin level. Serum κ free light chains were raised at 922.0 mg/l (3.3–19.4), λ 5.6 mg/l (5.7–26.3) and κ/λ ratio was 164.64 (0.26–1.65). The serum creatine kinase level was persistently high at 668 U/l, 24-hour urine total protein level was 0.5 g (<0.2) and κ Bence Jones protein was detected. There were no oligoclonal bands on urine electrophoresis. Bone marrow trephine biopsy was consistent with multiple myeloma. Skeletal survey showed no evidence of myeloma. Serum amyloid P scan showed no visceral amyloid deposition.
The diagnosis was systemic amyloidosis of light chain (AL) type, with possible underlying myeloma. The patient was given the combination of bortezomib (Velcade), cyclophosphamide and dexamethasone (according to the National Amyloidosis Centre protocol).4 The symptoms of carpal tunnel syndrome resolved without surgical intervention.
The patient presented with carpal tunnel syndrome but the systemic symptoms and proximal muscle weakness pointed to a systemic illness; muscle biopsy showed this illness, to our surprise, to be amyloidosis.
Amyloidosis results from deposition of insoluble amyloid protein in extracellular spaces of tissues and organs, also causing deposition in the carpal tunnel ligaments. It gives a characteristic Congo red staining on histopathological analysis with apple-green birefringence when viewed under polarised light.5 The nature of the amyloid precursor protein determines whether the amyloid is deposited locally or throughout the whole body. Any organ apart from the brain can be involved in amyloid depositions in systemic amyloidosis AL type. The most common sites are kidney, liver, heart and lungs, but soft tissue deposition also occurs in the tongue (macroglossia), submandibular glands, lymph nodes, blood vessels, muscle tissue and joints.6 According to some authors, carpal tunnel syndrome is the first presentation in 15–20% of patients with amyloidosis AL type.7 8
Even when a patient presents with a clinical history that is strongly suggestive of carpal tunnel syndrome, it should be borne in mind that sometimes this can be part of a more widespread illness.
This article was reviewed by Lionel Ginsberg, London, UK.
Competing interests None.
Provenance and peer review Not commissioned; externally peer reviewed.