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Brain Advance Access originally published online on May 31, 2008
Brain 2008 131(7):1903-1911; doi:10.1093/brain/awn102
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© The Author (2008). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Sensory deficit in Parkinson's disease: evidence of a cutaneous denervation

Maria Nolano1, Vincenzo Provitera1, Anna Estraneo1, Mona M. Selim2, Giuseppe Caporaso1, Annamaria Stancanelli1, Anna Maria Saltalamacchia1, Bernardo Lanzillo1 and Lucio Santoro3

1Neurology Division ‘Salvatore Maugeri’ Foundation – Medical Center of Telese Terme (BN) Italy, 2Department of Neurology, University of Minnesota, Minneapolis, MN, USA and 3Department of Neurological Sciences, University of Naples ‘Federico II’ Italy

Correspondence to: Maria Nolano MD, PhD, Neurology Department ‘S. Maugeri’ Foundation, Via Bagni Vecchi, 1 - 82037 Telese Terme (BN), Italy. E-mail: maria.nolano{at}fsm.it

Sensory disturbances are part of the clinical picture of Parkinson's disease. Abnormalities in sensory processing, through a basal ganglia involvement, are thought to be responsible for the sensory dysfunction since sensory nerve conduction velocity (NCV) is usually normal. However, NCV does not examine small fibres or terminal endings of large sensory fibres, whereas skin biopsy is more suitable for these purposes. To evaluate peripheral sensory nerves in Parkinson's disease, we studied cutaneous free and encapsulated sensory nerve endings in 18 patients and 30 healthy controls using 3-mm punch biopsies from glabrous and hairy skin. Ten patients had additional skin biopsies from the contralateral side. Further evaluation included NCV and Quantitative Sensory Testing. Parkinson's disease patients showed a significant increase in tactile and thermal thresholds (P < 0.01), a significant reduction in mechanical pain perception (P < 0.01) and significant loss of epidermal nerve fibres (ENFs) and Meissner corpuscles (MCs) (P < 0.01). In patients with bilateral biopsies, loss of pain perception and ENFs was higher on the more affected side (P < 0.01). We found evidence suggesting attempts at counteracting degenerative processes as increased branching, sprouting of nerves and enlargement of the vascular bed. Morphological and functional findings did not correlate with age or disease duration. Disease severity correlated with loss of MCs and reduction in cold perception and pain perception. We demonstrated a peripheral deafferentation in Parkinson's disease that could play a major role in the pathogenesis of the sensory dysfunction.

Key Words: Parkinson's disease; pain; skin biopsy; Meissner's corpuscles; peripheral nervous system

Abbreviations: ENFs, epidermal nerve fibres; IMEs, intrapapillary myelinated endings; MCs, Meissner's corpuscles; NCV, nerve conduction velocity; QST, quantitative sensory testing; SNAP, sensory nerve action potential

Received December 3, 2007. Revised March 5, 2008. Accepted May 1, 2008.


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