TNF Clinical Neurophysiology Group (PI Krishnan)

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Research Interests

Our work is at the forefront of a relatively new research field in human neurophysiology, studies of axonal excitability and its disorders. Measurements of excitability provide information regarding the activity of ion channels, energy-dependent pumps and ion exchange processes activated during impulse conduction. Abnormalities of ion channel function are a major factor in many neurological diseases, including peripheral neuropathy, motor neurone disease, multiple sclerosis and epilepsy. Excitability techniques are clinical methods of assessing nerve function, which we apply to patients with neurological disease. Arun Krishnan is a consultant Neurologist at Prince of Wales Hospital and patients are recruited from clinics run at the hospital. In addition to investigating causes of neurological disease, we also conduct clinical trials of new treatments for these conditions, based on the findings of our basic research. Our work is conducted in conjunction with research groups led by Professor Matthew Kiernan at the Prince of Wales Clinical School and Prince of Wales Medical Research Institute and Dr Cindy Lin in the Department of Exercise Physiology at UNSW.

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Collaborations

We have extensive local, national and international collaborators who are involved in excitability research. Within Prince of Wales Hospital, we have collaborations with the Departments of Renal Medicine (Prof Bruce Pussell), Endocrinology (Dr Ann Poynten), Medical Oncology (Prof David Goldstein and Prof Michael Friedlander) and Rehabilitation Medicine (Dr Pesi Katrak). Our collaborative studies with these departments have focussed on novel methods for diagnosing and treating neurological complications of systemic diseases, including diabetes, renal disease and cancer. Our collaborations also extend to the Central and Western Clinical Schools of the University of Sydney (Professor David Burke and Dr Steve Vucic respectively) and the George Institute for International Heath (Dr Meg Jardine). We also have a long-standing collaboration with Prof Hugh Bostock of the Institute of Neurology, London, the inventor of protocols for nerve excitability testing.

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Current Projects

• Effects of strict K+ restriction and dialysis treatments on neurological function in chronic kidney disease
• Natural history of axonal ion channel dysfunction in human diabetic neuropathy
• Quality of life in metabolic neuropathies.
• New methods for diagnosis and treatment of chemotherapy-induced neuropathy.
• Neuroprotective strategies for amyotrophic lateral sclerosis
• Cortical and peripheral nerve plasticity in stroke patients
• Ion channel dysfunction in central and peripheral demyelination.

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Funding

• NHMRC
• Brain Foundation
• Ramaciotti Foundation
• Royal Australasian College of Physicians
• Pfizer Neuroscience Grants

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Projects for PhD students

A number of projects are available for PhD students to work in the TNF.
Please, contact Dr. Arun Krishnan for details.

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Key Publications

1. Park SB, Lin CS, Krishnan AV, Friedlander ML, Lewis CR, Kiernan MC. Early, progressive, and sustained dysfunction of sensory axons underlies paclitaxel-induced neuropathy. Muscle Nerve. 2011 Mar;43(3):367-74.
2. Cheah BC, Vucic S, Krishnan AV, Boland RA, Kiernan MC. Neurophysiological index as a biomarker for ALS progression: validity of mixed effects models. Amyotroph Lateral Scler. 2011 Jan;12(1):33-8.
3. Park SB, Lin CS, Krishnan AV, Goldstein D, Friedlander ML, Kiernan MC. Utilizing natural activity to dissect the pathophysiology of acute oxaliplatin-induced neuropathy. Exp Neurol. 2011 Jan;227(1):120-7.
4. Krishnan AV, Park SB, Payne M, Lin CS, Vucic S, Kiernan MC. Regional differences in ulnar nerve excitability may predispose to the development of entrapment neuropathy. Clin Neurophysiol. 2011 Jan;122(1):194-8.
5. Park, S. B.; Lin, C. S.; Krishnan, A. V.; Goldstein, D.; Friedlander, M. L.; Kiernan, M. C. Oxaliplatin-induced neurotoxicity: changes in axonal excitability precede development of neuropathy. Brain (2009) 132 Pt 10 2712-23
6. Krishnan, A. V.; Kiernan, M. C. Neurological complications of chronic kidney disease. Nature Reviews Neurology (2009) 5 10 542-51
7. Krishnan, A. V.; Lin, C. S.; Park, S. B.; Kiernan, M. C. Axonal ion channels from bench to bedside: a translational neuroscience perspective. Progress in Neurobiology (2009) 89 3 288-313
8. Krishnan, A. V.; Lin, C. S.; Park, S. B.; Kiernan, M. C. Assessment of nerve excitability in toxic and metabolic neuropathies. Journal of the Peripheral Nervous System (2008) 13 1 7-26
9. Park, S. B.; Goldstein, D.; Lin, C. S.; Krishnan, A. V.; Friedlander, M. L.; Kiernan, M. C. Acute abnormalities of sensory nerve function associated with oxaliplatin-induced neurotoxicity. Journal of Clinical Oncology (2009) 27 8 1243-9
10. Krishnan, A. V.; Lin, C. S.; Kiernan, M. C. Activity-dependent excitability changes suggest Na+/K+ pump dysfunction in diabetic neuropathy. Brain (2008) 131 Pt 5 1209-16
11. Lin, C. S.; Krishnan, A. V.; Lee, M. J.; Zagami, A. S.; You, H. L.; Yang, C. C.; Bostock, H.; Kiernan, M. C. Nerve function and dysfunction in acute intermittent porphyria. Brain (2008) 131 Pt 9 2510-9
12. Krishnan, A. V.; Phoon, R. K.; Pussell, B. A.; Charlesworth, J. A.; Kiernan, M. C. Sensory nerve excitability and neuropathy in end stage kidney disease. Journal of Neurology, Neurosurgery & Psychiatry (2006) 77 4 548-51
13. Krishnan, A. V.; Goldstein, D.; Friedlander, M.; Kiernan, M. C. Oxaliplatin and axonal Na+ channel function in vivo. Clinical Cancer Research (2006) 12 15 4481-4
14. Krishnan, A. V.; Phoon, R. K.; Pussell, B. A.; Charlesworth, J. A.; Bostock, H.; Kiernan, M. C. Ischaemia induces paradoxical changes in axonal excitability in end-stage kidney disease. Brain (2006) 129 Pt 6 1585-92
15. Kiernan, M. C.; Krishnan, A. V.; Lin, C. S.; Burke, D.; Berkovic, S. F. Mutation in the Na+ channel subunit SCN1B produces paradoxical changes in peripheral nerve excitability. Brain (2005) 128 Pt 8 1841-6
16. Krishnan, A. V.; Colebatch, J. G.; Kiernan, M. C. Hypokalemic weakness in hyperaldosteronism: activity-dependent conduction block. Neurology (2005) 65 8 1309-12
17. Krishnan, A. V.; Kiernan, M. C. Altered nerve excitability properties in established diabetic neuropathy. Brain (2005) 128 Pt 5 1178-87
18. Krishnan, A.V; Phoon, R.K; Pussell, B.A.; Charlesworth, J.A.; Bostock, H.; Kiernan, M. C. Altered motor nerve excitability in end-stage kidney disease. Brain (2005) 128 9 2164-2174