Clinical and neuropathological parameters affecting the diagnostic yield of nerve biopsy

Abstract

The value of nerve biopsy in the investigation of peripheral neuropathies is an important and controversial issue, partially obscured by the large variations in the diagnostic yield routinely reported for this procedure. The aim of this study was to evaluate the clinical and neuropathological parameters affecting the yield of nerve biopsy. We compared the experience of two independent neuropathology laboratories with different patient recruitment and neuropathological methods over 11 years (01/1987–12/1997). Clinicopathological correlations were studied retrospectively in 355 patients. Using the same criteria of evaluation, contributive biopsies accounted for 35.5% in one laboratory, and 47.3% in the other. Clinical parameters affecting the yield of nerve biopsy were: (a) the presumptive diagnosis at time of referral for biopsy; (b) the distribution of symptoms; and (c) the interval between disease onset and biopsy. Greater yield was associated with clinically suspected vasculitis, inflammatory demyelinating neuropathy or hereditary sensorimotor neuropathies. Contributive findings were more often reported with multifocal or asymmetrical presentations, and onset-to-biopsy interval of less than 6 months. The contribution of nerve biopsy varied according to neuropathological techniques: (a) serial sections on frozen, paraffin-embedded and resin-embedded material improved sensitivity for interstitial pathology; (b) combined muscle biopsy increased sensitivity in the detection of vasculitis; and (c) teasing of nerve fibers added critical information to other classical techniques in only 4/102 cases.

Introduction

In the developed world, the prevalence of polyneuropathy is estimated at 3.4–3.6% in the elderly [1], [2]. Metabolic, toxic and nutritional causes are responsible for the majority of neuropathies in the general population and also account for 50% of cases in selected series from general hospitals [2], [3]. Among the 10–20% of cases that remain cryptogenic despite extensive investigation [4], [5], [6], [7], [8], patients with disabling peripheral neuropathy of recent onset or progression are potential candidates for a nerve biopsy [9], [10], [11], [12].

Nerve biopsy is of major value in the diagnosis of interstitial pathologies such as vasculitis, infiltration by inflammatory or neoplastic cells, or amyloidosis [9], [10], [11], [13]. Nerve biopsies also permit the recognition of neuropathies predominantly affecting small diameter nerve fibers, which may manifest only subtle electrophysiological abnormalities. The role of nerve biopsy in the diagnosis of hereditary conditions such as hereditary motor and sensory neuropathies (HMSN) and metabolic inherited disease has recently been reconsidered due to development of molecular genetic analysis of lymphocytes, biochemical screening and/or availability of alternative sites of biopsy [3], [10], [13], [14], [15], [16]. The value of microscopic examination in the recognition of chronic inflammatory demyelinating polyneuropathies (CIDP) is a matter of debate due to the lack of specificity of most histological findings in CIDP [13], [17], [18], [19], [20], [21].

The use of nerve biopsy is limited by postoperative sensory loss, immediate postoperative pain (reported by 30–50% of patients) and lasting discomfort described by 10% at 1 year [10], [22], [23], [24], [25], [26], [27], [28]. Major complications such as delayed healing, wound infection or neuroma formation are currently reported in 1% of patients [13], [22], [23] although some authors report an incidence of complications as high as 22% [28].

Because of these adverse effects, the practice of nerve biopsy has been currently challenged by a pre-biopsy therapeutic trial or non-invasive repeated diagnostic evaluation. It is therefore imperative to assess the yield of nerve biopsy. Previous studies have reported a large spectrum of results, probably due to differences in patient selection and neuropathological techniques. It is the aim of this study to evaluate how much these clinical and neuropathological parameters modify the proportion of contributive biopsies.

We reviewed the experience of two separate laboratories of neuropathology (Born-Bunge Foundation, University of Antwerp (BBF) and University Hospital of Liège (ULg)) over a period of 11 years (1987–1997). Both laboratories recorded a gradual increase in the annual number of nerve biopsies. In this retrospective study, we assessed the value of nerve biopsy on the basis of clinicopathological correlations of 355 cases. The results of both laboratories were compared with reference to differences in patient recruitment and neuropathological procedures.