Ischaemic sensitivity of axons in carpal tunnel syndrome
S. Eric Han
Prince of Wales Medical Research Institute & Prince of Wales Clinical School, University of New South Wales, Barker Street, Randwick NSW, Australia
Search for more papers by this authorRobert A. Boland
Prince of Wales Medical Research Institute & Prince of Wales Clinical School, University of New South Wales, Barker Street, Randwick NSW, Australia
Search for more papers by this authorArun V. Krishnan
Prince of Wales Medical Research Institute & Prince of Wales Clinical School, University of New South Wales, Barker Street, Randwick NSW, Australia
Search for more papers by this authorSteve Vucic
Prince of Wales Medical Research Institute & Prince of Wales Clinical School, University of New South Wales, Barker Street, Randwick NSW, Australia
Search for more papers by this authorCindy S.-Y. Lin
Prince of Wales Medical Research Institute & Prince of Wales Clinical School, University of New South Wales, Barker Street, Randwick NSW, Australia
Search for more papers by this authorCorresponding Author
Matthew C. Kiernan
Prince of Wales Medical Research Institute & Prince of Wales Clinical School, University of New South Wales, Barker Street, Randwick NSW, Australia
A/Prof. Matthew C. Kiernan, Prince of Wales Medical Research Institute, Barker Street, Randwick, Sydney, NSW 2031 Australia. Tel: +61 2 9382 2422; Fax: + 61 2 9382 2437; E-mail: [email protected]Search for more papers by this authorS. Eric Han
Prince of Wales Medical Research Institute & Prince of Wales Clinical School, University of New South Wales, Barker Street, Randwick NSW, Australia
Search for more papers by this authorRobert A. Boland
Prince of Wales Medical Research Institute & Prince of Wales Clinical School, University of New South Wales, Barker Street, Randwick NSW, Australia
Search for more papers by this authorArun V. Krishnan
Prince of Wales Medical Research Institute & Prince of Wales Clinical School, University of New South Wales, Barker Street, Randwick NSW, Australia
Search for more papers by this authorSteve Vucic
Prince of Wales Medical Research Institute & Prince of Wales Clinical School, University of New South Wales, Barker Street, Randwick NSW, Australia
Search for more papers by this authorCindy S.-Y. Lin
Prince of Wales Medical Research Institute & Prince of Wales Clinical School, University of New South Wales, Barker Street, Randwick NSW, Australia
Search for more papers by this authorCorresponding Author
Matthew C. Kiernan
Prince of Wales Medical Research Institute & Prince of Wales Clinical School, University of New South Wales, Barker Street, Randwick NSW, Australia
A/Prof. Matthew C. Kiernan, Prince of Wales Medical Research Institute, Barker Street, Randwick, Sydney, NSW 2031 Australia. Tel: +61 2 9382 2422; Fax: + 61 2 9382 2437; E-mail: [email protected]Search for more papers by this authorAbstract
Although carpal tunnel syndrome (CTS) is the most common human entrapment neuropathy characterized by paraesthesiae and numbness with nocturnal exacerbation, the mechanisms underlying the generation of these symptoms remain unclear. Consequently, the aim of the present study was to investigate the relationship between changes in axonal excitability and the development of neurological symptoms in response to an ischaemic insult in CTS patients. Sensory and motor excitability were measured in 10 CTS patients and compared with 10 healthy controls, with participants asked to report symptom generation and intensity during the development of limb ischaemia. To induce ischaemia, a sphygmomanometer was inflated above the elbow and maintained at 200 mmHg for 10 min. During ischaemia there were decreases in axonal threshold, with less overall reduction in CTS patients when compared with controls. Associated with these differences in threshold, both sensory (p < 0.001) and motor (p < 0.05) refractoriness increased dramatically in CTS patients. This prominent increase in refractoriness was accompanied by a significant reduction in compound sensory action potentials and compound motor action potentials amplitudes for CTS patients when compared with controls (p < 0.05). These changes in axonal excitability resulted in a higher intensity of numbness and paraesthesiae reported by CTS patients during ischaemia. The present study has established differences in the nerve excitability and symptom development during ischaemia for patients with mild and moderate CTS, and may suggest that axons in the median nerve of CTS patients have an altered functional capacity to respond to an ischaemic insult, further contributing to nocturnal exacerbation of their symptoms.
References
- Boland RA, Kiernan MC (2009). Assessing the accuracy of a combination of clinical tests for identifying carpal tunnel syndrome. J Clin Neurosci 16: 929–933.
- Bostock H (1983). The strength-duration relationship for excitation of myelinated nerve: computed dependence on membrane parameters. J Physiol 341: 59–74.
- Bostock H, Grafe P (1985). Activity-dependent excitability changes in normal and demyelinated rat spinal root axons. J Physiol 365: 239–257.
- Bostock H, Rothwell JC (1997). Latent addition in motor and sensory fibres of human peripheral nerve. J Physiol 498: 277–294.
- Bostock H, Baker M, Grafe P, Reid G (1991a). Changes in excitability and accommodation of human motor axons following brief periods of ischaemia. J Physiol 441: 513–535.
- Bostock H, Baker M, Reid G (1991b). Changes in excitability of human motor axons underlying post-ischaemic fasciculations: evidence for two stable states. J Physiol 441: 537–557.
- Bostock H, Burke D, Hales JP (1994). Differences in behaviour of sensory and motor axons following release of ischaemia. Brain 117: 225–234.
-
Bostock H,
Cikurel K,
Burke D (1998). Threshold tracking techniques in the study of human peripheral nerve.
Muscle Nerve
21: 137–158.
10.1002/(SICI)1097-4598(199802)21:2<137::AID-MUS1>3.0.CO;2-C CAS PubMed Web of Science® Google Scholar
-
Brain WR,
Wright AD,
Wilkinson M (1947). Spontaneous compression of both median nerves in the carpal tunnel six cases treated surgically.
The Lancet
249: 277–282.
10.1016/S0140-6736(47)90093-7 Google Scholar
- Brown WF (1984). The Physiological and Technical Basis of Electromyography. Butterworths, Boston.
- Burke D, Skuse NF, Lethlean AK (1974). Sensory conduction of the sural nerve in polyneuropathy. J Neurol, Neurosurg Psychiatr 37: 647–652.
- Cappelen-Smith C, Lin CSY, Burke D (2003). Activity-dependent hyperpolarization and impulse conduction in motor axons in patients with carpal tunnel syndrome. Brain 126: 1001–1008.
- Dawson DM, Hallett M, Millender LH (1990). Entrapment Neuropathies, 2nd Edn. Little Brown, Boston.
- Gelberman RH, Hergenroeder PT, Hargens AR, Lundborg GN, Akeson WH (1981). The carpal tunnel syndrome. A study of carpal canal pressures. J Bone Joint Surg Am 63: 380–383.
- Gerritsen AA, De Krom MC, Struijs MA, Scholten RJ, De Vet HC, Bouter LM (2002). Conservative treatment options for carpal tunnel syndrome: a systematic review of randomised controlled trials. J Neurol 249: 272–280.
- Gilliatt RW (1980). Chronic nerve compression and entrapment. In: The Physiology of Peripheral Nerve Disease. AJ Sumner (Ed). W.B. Saunders, Philadelphia, pp 316–339.
- Han SE, Boland RA, Krishnan AV, Vucic S, Lin CS, Kiernan MC (2008). Changes in human sensory axonal excitability induced by an ischaemic insult. Clin Neurophysiol 119: 2054–2063.
- Hodgkin AL, Huxley AF (1952). A quantitative description of membrane current and its application to conduction and excitation in nerve. J Physiol 117: 500–544.
- Ikemoto T, Tani T, Taniguchi S, Ikeuchi M, Kimura J (2009). Effects of experimental focal compression on excitability of human median motor axons. Clin Neurophysiol 120: 342–347.
- Jablecki CK, Andary MT, Floeter MK, Miller RG, Quartly CA, Vennix MJ, Wilson JR (2002). Practice parameter: electrodiagnostic studies in carpal tunnel syndrome. Report of the American Association of Electrodiagnostic Medicine, American Academy of Neurology, and the American Academy of Physical Medicine and Rehabilitation. Neurology 58: 1589–1592.
- Kiernan MC, Bostock H (2000). Effects of membrane polarization and ischaemia on the excitability properties of human motor axons. Brain 123: 2542–2551.
- Kiernan MC, Mogyoros I, Burke D (1996). Changes in excitability and impulse transmission following prolonged repetitive activity in normal subjects and patients with a focal nerve lesion. Brain 119: 2029–2037.
- Kiernan MC, Mogyoros I, Hales JP, Gracies JM, Burke D (1997). Excitability changes in human cutaneous afferents induced by prolonged repetitive axonal activity. J Physiol 500: 255–264.
- Kiernan MC, Mogyoros I, Burke D (1999). Conduction block in carpal tunnel syndrome. Brain 122: 933–941.
-
Kiernan MC,
Burke D,
Andersen KV,
Bostock H (2000). Multiple measures of axonal excitability: a new approach in clinical testing.
Muscle Nerve
23: 399–409.
10.1002/(SICI)1097-4598(200003)23:3<399::AID-MUS12>3.0.CO;2-G CAS PubMed Web of Science® Google Scholar
- Kiernan MC, Lin CS, Andersen KV, Murray NM, Bostock H (2001). Clinical evaluation of excitability measures in sensory nerve. Muscle Nerve 24: 883–892.
- Kiernan MC, Lin CSY, Burke D (2004). Differences in activity-dependent hyperpolarization in human sensory and motor axons. J Physiol 558: 341–349.
- Kimura J (1979). The carpal tunnel syndrome: localization of conduction abnormalities within the distal segment of the median nerve. Brain 102: 619–635.
- Kimura J (1989). Electrodiagnosis in Diseases of Nerve and Muscle: Principles and Practice, 2nd Edn. F.A. Davis, Philadelphia.
-
Kremer M,
Gilliatt RW,
Golding JS,
Wilson TG (1953). Acroparaesthesiae in the carpal-tunnel syndrome.
Lancet
262: 590–595.
10.1016/S0140-6736(53)90326-2 Google Scholar
- Krishnan AV, Kiernan MC (2005). Altered nerve excitability properties in established diabetic neuropathy. Brain 128: 1178–1187.
- Krishnan AV, Phoon RK, Pussell BA, Charlesworth JA, Kiernan MC (2006). Sensory nerve excitability and neuropathy in end stage kidney disease. J Neurol Neurosurg Psychiatr 77: 548–551.
- Krishnan AV, Lin CS, Kiernan MC (2008). Activity-dependent excitability changes suggest Na+/K+ pump dysfunction in diabetic neuropathy. Brain 131: 1209–1216.
- Levine DW, Simmons BP, Koris MJ, Daltroy LH, Hohl GG, Fossel AH, Katz JN (1993). A self-administered questionnaire for the assessment of severity of symptoms and functional status in carpal tunnel syndrome. J Bone Joint Surg Am 75: 1585–1592.
- Lin CS, Mogyoros I, Kuwabara S, Cappelen-Smith C, Burke D (2001). Differences in responses of cutaneous afferents in the human median and sural nerves to ischemia. Muscle Nerve 24: 1503–1509.
- Lin CS, Grosskreutz J, Burke D (2002a). Sodium channel function and the excitability of human cutaneous afferents during ischaemia. J Physiol 538: 435–446.
- Lin CSY, Kuwabara S, Cappelen-Smith C, Burke D (2002b). Responses of human sensory and motor axons to the release of ischaemia and to hyperpolarizing currents. J Physiol 541: 1025–1039.
- Miller TA, Kiernan MC, Mogyoros I, Burke D (1995). Activity-dependent changes in impulse conduction in normal human cutaneous axons. Brain 118: 1217–1224.
- Miller TA, Kiernan MC, Mogyoros I, Burke D (1996). Activity-dependent changes in impulse conduction in a focal nerve lesion. Brain 119: 429–437.
- Mogyoros I, Kiernan MC, Burke D (1996). Strength-duration properties of human peripheral nerve. Brain 119: 439–447.
- Mogyoros I, Kiernan MC, Burke D (1997). Strength-duration properties of sensory and motor axons in carpal tunnel syndrome. Muscle Nerve 20: 508–510.
- Morita K, David G, Barrett JN, Barrett EF (1993). Posttetanic hyperpolarization produced by electrogenic Na(+)-K+ pump in lizard axons impaled near their motor terminals. J Neurophysiol 70: 1874–1884.
- Ochoa J, Marotte L (1973). The nature of the nerve lesion caused by chronic entrapment in the guinea-pig. J Neurol Sci 19: 491–495.
- Ochoa J, Fowler TJ, Gilliatt RW (1972). Anatomical changes in peripheral nerves compressed by a pneumatic tourniquet. J Anat 113: 433–455.
- Phalen GS, Gardner WJ, La Londe AA (1950). Neuropathy of the median nerve due to compression beneath the transverse carpal ligament. J Bone Joint Surg Am 32A: 109–112.
- Rydevik B, Lundborg G, Bagge U (1981). Effects of graded compression on intraneural blood blow. An in vivo study on rabbit tibial nerve. J Hand Surg [Am] 6: 3–12.
- Schwarz JR, Glassmeier G, Cooper EC, Kao TC, Nodera H, Tabuena D, Kaji R, Bostock H (2006). KCNQ channels mediate IKs, a slow K+ current regulating excitability in the rat node of Ranvier. J Physiol 573: 17–34.
- Vagg R, Mogyoros I, Kiernan MC, Burke D (1998). Activity-dependent hyperpolarization of human motor axons produced by natural activity. J Physiol 507: 919–925.
- Weiss G (1901). “Sur la possibilité de rendre comparables entre eux les appareils servant à l’excitation électrique” (On the possibility to make mutually comparable devices serving for electrical excitation). Arch Ital Biol 35: 413–446.
Citing Literature
