Clinical Trial: Cutaneous Denervation in Alcoholic Neuropathy

Study Status: Completed
Recruit Status: Unknown status
Study Type: Observational

Official Title: Cutaneous Denervation in Alcoholic Neuropathy

Brief Summary: Peripheral neuropathy is a frequent neurological complication of chronic alcoholism. Most studies evaluated large-fiber involvement by nerve conduction studies (NCS). Since previous studies document the predominant injury of small myelinated and unmyelinated fibers in patients with alcoholic neuropathy, it will be imperative to know their prevalence and clinical significance. Moreover, the pathogenesis of alcoholic neuropathy, especially the roles of ethanol and its metabolites and thiamine, remains elusive. This proposal will be designed to understand the extent and clinical significance of cutaneous nerve degeneration in the skin of alcoholic patients and to investigate its pathogenesis. We will investigate cutaneous innervation by 3 mm punch skin biopsies with immunohistochemistry for protein gene product 9.5 and quantifying epidermal nerve density (END) in alcoholic patients. Patients will undergo clinical evaluation, quantitative sensory testing (QST), nerve conduction studies (NCS), and tests of sympathetic skin response (SSR) and beat-to-beat RR interval variability (RRIV). The prevalence of peripheral neuropathy in chronic alcoholic patients with emphasis on small-fiber involvement will be first evaluated. The sensitivity of punch skin biopsy, QST, SSR and RRIV tests, and NCS will be compared, and the correlations between END and psychophysic and electrodiagnostic parameters will be discussed. Subsequently, we will elucidate the clinical significance of END reduction in alcoholic patients. Patients with evidences of involvement of central nervous system will be excluded, and END will be correlated with clinical manifestations and neurological deficits. Finally, the role of ethanol and thiamine in alcoholic neuropathy will be further studied. To clarify the role of thiamine in alcoholic neuropathy, we will examine whether it has influences on small-fiber degeneration. This may provide important information in understanding the pathogenesis and designing optim

Detailed Summary:

Alcoholic patients and control subjects. Alcoholic patients will be recruited from neurologic clinics and ward at the Far Eastern Memorial Hospital, Taipei, Taiwan. A detailed clinical history that includes daily alcohol consumption, daily dietary intake, lifestyle, and occupation will be obtained from patients as well as their families. The inclusion criteria include daily uptake of at least 100 g ethanol for more than 3 years prior to the onset of neuropathic symptoms (Behse and Buchthal, 1977). All patients will undergo clinical and neurologic assessment, cranial MRI or CT, and neuropsychological evaluation to rule out CNS disorders, which interfere the evaluation of neuropathic symptoms and signs and psychophysic test. Laboratory investigations will include complete blood count, fasting plasma glucose, hemoglobin A1C, liver and renal function tests, ethanol level, tumor markers, antinuclear antibodies, complement factors, serum protein electrophoresis, thyroid function, human immunodeficiency virus, hepatitis virus, and vitamin B12 level. Thiamine status will be assessed at the time of the first referral to the hospital by measuring total thiamine concentration in whole blood by high performance liquid chromatography, as described elsewhere (Koike et al., 2001 and 2003). None of the patients will administrate thiamine at the time of determination. Age- and gender-matched control subjects will be retrieved from our database, who will be evaluated by detailed questionnaires and neurological examinations to exclude any neurological disorder or clinical neuropathy (McCarthy et al., 1995).

Skin biopsy. Skin biopsy will be performed following established procedures after informed consent has been obtained (McCarthy et al., 1995; Pan et al., 2003; Shun et al., 2004). Under local anesthesia with 2% lidocaine, punches 3mm in diameter will be taken from the following locations:
Sponsor: Far Eastern Memorial Hospital

Current Primary Outcome:

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Information By: Far Eastern Memorial Hospital

Dates:
Date Received: September 11, 2005
Date Started: January 2005
Date Completion: December 2005
Last Updated: September 11, 2005
Last Verified: September 2005