Peripheral Autonomic Neuropathy: Diagnostic Contribution of Skin Biopsy

Abstract Skin biopsy has gained widespread use for the diagnosis of somatic small-fiber neuropathy, but it also provides information on sympathetic fiber morphology. We aimed to ascertain the diagnostic accuracy of skin biopsy in disclosing sympathetic nerve abnormalities in patients with autonomic neuropathy. Peripheral nerve fiber autonomic involvement was confirmed by routine autonomic laboratory test abnormalities. Punch skin biopsies were taken from the thigh and lower leg of 28 patients with various types of autonomic neuropathy for quantitative evaluation of skin autonomic innervation. Results were compared with scores obtained from 32 age-matched healthy controls and 25 patients with somatic neuropathy. The autonomic cutoff score was calculated using the receiver operating characteristic curve analysis. Skin biopsy disclosed a significant autonomic innervation decrease in autonomic neuropathy patients versus controls and somatic neuropathy patients. Autonomic innervation density was abnormal in 96% of patients in the lower leg and in 79% of patients in the thigh. The abnormal findings disclosed by routine autonomic tests ranged from 48% to 82%. These data indicate the high sensitivity and specificity of skin biopsy in detecting sympathetic abnormalities; this method should be useful for the diagnosis of autonomic neuropathy, together with currently available routine autonomic testing.

[1]  B. Adams-Huet,et al.  A Unique Manifestation of Pupillary Fatigue in Autoimmune Autonomic Ganglionopathy. , 2012, Archives of neurology.

[2]  C. Chao,et al.  Quantitation of Sudomotor Innervation in Skin Biopsies of Patients With Diabetic Neuropathy , 2011, Journal of neuropathology and experimental neurology.

[3]  L. Santoro,et al.  Quantification of pilomotor nerves , 2010, Neurology.

[4]  M. Elam,et al.  Autonomic innervation in multiple system atrophy and pure autonomic failure , 2010, Journal of Neurology, Neurosurgery & Psychiatry.

[5]  R. Freeman,et al.  Quantification of sudomotor innervation: A comparison of three methods , 2010, Muscle & nerve.

[6]  R. Mignani,et al.  Small fiber neuropathy in female patients with fabry disease , 2010, Muscle & nerve.

[7]  D. Goldstein,et al.  Cardiac sympathetic hypo-innervation in familial dysautonomia , 2008, Clinical Autonomic Research.

[8]  P. Sandroni,et al.  Detection of small‐fiber neuropathy by sudomotor testing , 2006, Muscle & nerve.

[9]  G. Wendelschafer‐Crabb,et al.  Morphological features of nerves in skin biopsies , 2006, Journal of the Neurological Sciences.

[10]  Maria Nolano,et al.  Skin sympathetic adrenergic innervation: An immunofluorescence confocal study , 2006, Annals of neurology.

[11]  R. Baron,et al.  Is CRPS I a neuropathic pain syndrome? , 2006, Pain.

[12]  Agostino Baruzzi,et al.  Habituation of sympathetic sudomotor and vasomotor skin responses: neural and non-neural components in healthy subjects , 2005, Clinical Neurophysiology.

[13]  M. Nolano,et al.  Generalised anhidrosis: different lesion sites demonstrated by microneurography and skin biopsy , 2005, Journal of Neurology, Neurosurgery & Psychiatry.

[14]  R. Pop-Busui,et al.  Sympathetic dysfunction in type 1 diabetes: association with impaired myocardial blood flow reserve and diastolic dysfunction. , 2004, Journal of the American College of Cardiology.

[15]  William R Kennedy,et al.  Opportunities afforded by the study of unmyelinated nerves in skin and other organs , 2004, Muscle & nerve.

[16]  P. Kench,et al.  Cardiac autonomic neuropathy in the diabetic patient: does 123I-MIBG imaging have a role to play in early diagnosis? , 2004, Journal of nuclear medicine technology.

[17]  J. McArthur,et al.  Prospective evaluation of somatic and autonomic small fibers in selected autonomic neuropathies , 2004, Neurology.

[18]  S. Park,et al.  A case of incomplete postganglionic cholinergic dysautonomia , 2003, Journal of Neurology.

[19]  M. Schäfer,et al.  VIP and NPY Expression during Differentiation of Cholinergic and Noradrenergic Sympathetic Neurons a , 1998, Annals of the New York Academy of Sciences.

[20]  A. Langer,et al.  Relation of direct assessment of cardiac autonomic function with metaiodobenzylguanidine imaging to heart rate variability in diabetes mellitus. , 1997, The American journal of cardiology.

[21]  J. Mcleod,et al.  Autonomic neuropathy, II: Specific peripheral neuropathies , 1996, Journal of the Neurological Sciences.

[22]  O. Schnell,et al.  Reduced Myocardial 123I-Metaiodobenzylguanidine Uptake in Newly Diagnosed IDDM Patients , 1996, Diabetes.

[23]  D. Ziegler,et al.  Diabetic cardiovascular autonomic neuropathy: prognosis, diagnosis and treatment. , 1994, Diabetes/metabolism reviews.

[24]  E. Sforza,et al.  Cardiovascular autonomic dysfunction in normotensive awake subjects with obstructive sleep apnoea syndrome , 1994, Clinical Autonomic Research.

[25]  P A Low,et al.  Composite autonomic scoring scale for laboratory quantification of generalized autonomic failure. , 1993, Mayo Clinic proceedings.

[26]  G. Wendelschafer‐Crabb,et al.  The innervation of human epidermis , 1993, Journal of the Neurological Sciences.

[27]  J. Mcleod,et al.  Autonomic Dysfunction in Peripheral Nerve Disease , 1993, Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society.

[28]  D. Goldstein,et al.  Positron emission tomographic imaging of cardiac sympathetic innervation and function. , 1990, Circulation.

[29]  C. Jf,et al.  [Diabetic autonomic neuropathy]. , 1989, Atencion primaria.

[30]  Y. Harati,et al.  Sympathetic skin response in diabetic peripheral neuropathy , 1988, Muscle & nerve.

[31]  P. Dyck,et al.  Quantitative sudomotor axon reflex test in normal and neuropathic subjects , 1983, Annals of neurology.

[32]  S. Harik,et al.  Postganglionic cholinergic dysautonomia , 1977, Annals of neurology.

[33]  R. Freeman,et al.  Testing the autonomic nervous system. , 2013, Handbook of clinical neurology.

[34]  P. Lozeron,et al.  [Autonomic peripheral neuropathy]. , 2012, Presse medicale.

[35]  R. Pop-Busui.  Cardiac Autonomic Neuropathy in Diabetes A clinical perspective , 2010 .

[36]  R. Baron,et al.  Postganglionic cholinergic dysautonomia with incomplete recovery: A clinical, neurophysiological and immunological case study , 2004, Journal of Neurology.

[37]  Christopher J. Mathias,et al.  Investigation of autonomic disorders , 1992 .

[38]  P. Low,et al.  The sympathetic nervous system in diabetic neuropathy. A clinical and pathological study. , 1975, Brain : a journal of neurology.