Background. Established electrophysiological methods have limited clinical utility in the diagnosis of small fiber neuropathy. The cutaneous silent period (CSP) may be useful as a method for the evaluation of smaller and unmyelinated fiber dysfunctions. Hyperlipidemia is a very rare cause of small fiber neuropathy. In this study, hyperlipidemia and small fiber neuropathy in symptomatic patients with normal nerve conduction studies were evaluated with autonomic tests and cutaneous silent periods. Methods. Twenty-five patients with clinically suspected small fiber neuropathy and 23 healthy volunteers were included. CSP latency and duration, as well as CSP latency difference of the upper and lower extremities, were examined. Two tests were used to assess the autonomic nervous system, namely, the R-R interval variation test in basal and profound breath conditions and the sympathetic skin response. Results. Twenty-five patients with clinically suspected small fiber neuropathy and normal nerve conduction studies were compared with 23 controls. In the upper extremities, patients had prolonged CSP latencies ( ) and shortened CSP durations ( ), whereas in the lower extremities, patients had shortened CSP durations ( ). The expiration-to-inspiration ratios were also reduced in patients groups. There was no significant difference between sympathetic skin response latencies and amplitude of the case and control groups. Conclusion. Our findings indicate that CSP may become a useful technique for the assessment of small fiber neuropathy in hyperlipidemic patients. 1. Introduction Small fiber neuropathy (SFN) can be defined as generalized peripheral neuropathy, where small myelinated A-delta and unmyelinated C nerve fibers are specifically more affected alone or compared with large fibers. Patients with SFN refer to the neurology clinics with generally positive sensory complaints such as burning, stinging and pain in the feet, and/or autonomic symptoms. The neurological examination in SFN is either completely normal or just impaired pain-temperature sensation is found. A number of methods are required for early detection and treatment of SFN. The methods for assessing small fiber dysfunction are limited despite its clinical significance. Their clinical use is limited, since most of these methods are invasive or time consuming or require special equipment. While mainly pain and temperature sensations are affected in small fiber neuropathy, the manifestation may also be accompanied by autonomic dysfunction. In addition, routine nerve conduction studies showing the large
References
[1]
A. Uncini, T. Kujirai, B. Gluck, and S. Pullman, “Silent period induced by cutaneous stimulation,” Electroencephalography and Clinical Neurophysiology, vol. 81, no. 5, pp. 344–352, 1991.
[2]
M. Serrao, L. Parisi, F. Pierelli, and P. Rossi, “Cutaneous afferents mediating the cutaneous silent period in the upper limbs: evidences for a role of low-threshold sensory fibres,” Clinical Neurophysiology, vol. 112, no. 11, pp. 2007–2014, 2001.
[3]
M. Inghilleri, G. Cruccu, M. Argenta, L. Polidori, and M. Manfredi, “Silent period in upper limb muscles after noxious cutaneous stimulation in man,” Electroencephalography and Clinical Neurophysiology, vol. 105, no. 2, pp. 109–115, 1997.
[4]
W. J. Fessel, “Fat disorders and peripheral neuropathy,” Brain, vol. 94, no. 3, pp. 531–540, 1971.
[5]
U. Sandbank and J. J. Bubis, “Hyperlipemic neuropathy: experimental study,” Brain, vol. 96, no. 2, pp. 355–358, 1973.
[6]
P. G. McMannis, A. J. Windebank, and M. K？z？ltan, “Neuropathy associated with hyperlipidemia,” Neurology, vol. 44, pp. 2185–2186, 1994.
[7]
H. S. Kassem, S. T. Azar, M. S. Zantout, and R. A. Sawaya, “Hypertriglyceridemia and peripheral neuropathy in neurologically asymptomatic patients,” Neuroendocrinology Letters, vol. 26, no. 6, pp. 775–779, 2005.
[8]
W. S. David, Z. Mahdavi, M. Nance, and M. Khan, “Hyperlipidemia and neuropathy,” Electromyography and Clinical Neurophysiology, vol. 39, no. 4, pp. 227–230, 1999.
[9]
E. L. Feldman, M. J. Stevens, P. K. Thomas, M. B. Brown, N. Canal, and D. A. Greene, “A practical two-step quantitative clinical and electrophysiological assessment for the diagnosis and staging of diabetic neuropathy,” Diabetes Care, vol. 17, no. 11, pp. 1281–1289, 1994.
[10]
E. J. Bastyr III, K. L. Price, and V. Bril, “Development and validity testing of the neuropathy total symptom score-6: questionnaire for the study of sensory symptoms of diabetic peripheral neuropathy,” Clinical Therapeutics, vol. 27, no. 8, pp. 1278–1294, 2005.
[11]
I. Unal-Cevik, S. Sarioglu-Ay, and D. Evcik, “A comparison of the DN4 and LANSS questionnaires in the assessment of neuropathic pain: validity and reliability of the turkish version of DN4,” Journal of Pain, vol. 11, no. 11, pp. 1129–1135, 2010.
[12]
S. J. Oh, “Nerve conduction techniques,” in Clinical Electromyography: Nerve Conduction Studies, pp. 37–52, Lippincott Williams Wilkins, 3rd edition, 2002.
[13]
O. May and H. Arildsen, “Assessing cardiovascular autonomic neuropathy in diabetes mellitusHow many tests to use?” Journal of Diabetes and Its Complications, vol. 14, no. 1, pp. 7–12, 2000.
[14]
S. J. Oh, “Special nerve conduction techniques,” in Clinical Electromyography: Nerve Conduction Studies, pp. 447–503, Lippincott Williams & Wilkins, 3rd edition, 2002.
[15]
M. Kofler, “Functional organization of exteroceptive inhibition following nociceptive electrical fingertip stimulation in humans,” Clinical Neurophysiology, vol. 114, no. 6, pp. 973–980, 2003.
[16]
M. K. Floeter, “Cutaneous silent periods,” Muscle and Nerve, vol. 28, no. 4, pp. 391–401, 2003.
[17]
G. Lauria, M. Morbin, R. Lombardi et al., “Axonal swellings predict the degeneration of epidermal nerve fibers in painful neuropathies,” Neurology, vol. 61, no. 5, pp. 631–636, 2003.
[18]
C. H. Gibbons, J. W. Griffin, M. Polydefkis et al., “The utility of skin biopsy for prediction of progression in suspected small fiber neuropathy,” Neurology, vol. 66, no. 2, pp. 256–258, 2006.
[19]
D. N. Herrmann, M. L. Ferguson, V. Pannoni, R. L. Barbano, M. Stanton, and E. L. Logigian, “Plantar nerve AP and skin biopsy in sensory neuropathies with normal routine conduction studies,” Neurology, vol. 63, no. 5, pp. 879–885, 2004.
[20]
K. R. Sharma, D. Saadia, A. G. Facca, S. Resnick, and D. R. Ayyar, “Diagnostic role of deep tendon reflex latency measurement in small-fiber neuropathy,” Journal of the Peripheral Nervous System, vol. 12, no. 3, pp. 223–231, 2007.
[21]
G. Devigili, V. Tugnoli, P. Penza et al., “The diagnostic criteria for small fibre neuropathy: from symptoms to neuropathology,” Brain, vol. 131, no. 7, pp. 1912–1925, 2008.
[22]
B.-J. Kim, N.-H. Kim, S. G. Kim et al., “Utility of the cutaneous silent period in patients with diabetes mellitus,” Journal of the Neurological Sciences, vol. 293, no. 1-2, pp. 1–5, 2010.
[23]
P. D. Aravindan and M. Lioyed, “Scalp pain and hyperlipidemia,” International Journal of Clinical Practice, vol. 54, pp. 478–490, 2000.
[24]
T. D. Wiggin, K. A. Sullivan, R. Pop-Busui, A. Amato, A. A. F. Sima, and E. L. Feldman, “Elevated triglycerides correlate with progression of diabetic neuropathy,” Diabetes, vol. 58, no. 7, pp. 1634–1640, 2009.
[25]
A. A. Leis, “Conduction abnormalities detected by silent period testing,” Electroencephalography and Clinical Neurophysiology, vol. 93, no. 6, pp. 444–449, 1994.
[26]
N. A. Syed, F. Sandbrink, C. A. Luciano et al., “Cutaneous silent periods in patients with Fabry disease,” Muscle Nerve, vol. 23, pp. 1179–1186, 2000.
[27]
F. M. Corsi, S. Fausti, M. Serrao, C. Casali, L. Parisi, and G. Piazza, “Electromyographic mixed nerve and cutaneous silent period in evaluating the A-delta fibres in a patient with hereditary sensory-autonomic neuropathy,” Functional Neurology, vol. 17, no. 1, pp. 31–34, 2002.
[28]
M. Yaman, D. Uludüz, S. Yüksel, G. Pay, and M. E. Kiziltan, “The cutaneous silent period in diabetes mellitus,” Neuroscience Letters, vol. 419, pp. 258–262, 2007.
[29]
M. R. Onal, U. H. Ulas, O. Oz et al., “Cutaneous silent period changes in Type 2 diabetes mellitus patients with small fiber neuropathy,” Clinical Neurophysiology, vol. 121, no. 5, pp. 714–718, 2010.
