Diagnostic value of sural nerve biopsy in chronic inflammatory demyelinating polyneuropathy
Medical records were reviewed of patients from seven university hospitals in The Netherlands who underwent a sural nerve biopsybetween 1989 and 1994. Included in the study were patients inwhom CIDP was considered in the differential diagnosis beforesural nerve biopsy. Sural nerve biopsies were processed and assessed according to standard techniques, including teased fibre preparations.2 Electron microscopy was carried out when the neuropathologistconsidered that this was necessary. Excluded were patients with an appropriate history of drug or toxic exposure known to cause peripheral neuropathy, with a known family history of peripheral neuropathy, and with incomplete data on clinical signs and symptoms, blood tests, CSF tests, electrophysiological studies, biopsy studies, response to treatment, and clinical course after biopsy.
ASSESSMENT OF CLINICAL FEATURES AND SURAL NERVE BIOPSY
Six clinical features, from the period before sural nerve biopsy was performed, were extracted from the medical records. The features were the presence of (1) relapsing course; (2) symmetricsensorimotor neuropathy in arms and legs; (3) areflexia of allfour limbs; (4) raised CSF protein concentration (moderately (0.5-1.0 g/l) and highly (>1.0 g/l) raised); (5) neurophysiological studies consistent with CIDP, and (6) relevant comorbidity or relevant abnormalities in laboratory tests that were sufficient to explain the occurrence of peripheral neuropathy. Neurophysiological studieswere considered consistent with CIDP if there was a non-uniform pattern of abnormalities and if three of the following four abnormalities were shown: (a) slowed nerve conduction velocity, defined as less than 75% of the lower limit of normal, of at least one motor nervein the arms; (b) partial conduction block in one or more motor nerves, defined as difference of at least 30% in compound muscle action potential (peak to peak) recorded after stimulation at proximal and distal segments and provided that the potential after distal stimulation is more than 1.0 mV peak to peak; (c) prolongeddistal latency of more than 130% of the upper limit of normalin one or more motor nerves in the arms; and (d) prolonged F wave of more than 130% of the upper limit of normal in one or more motor nerves. The abnormalities were modified from the neurophysiological criteria of Albers and Kelly.11 Instead of the presence of decreased nerve conduction velocity in at least two motor nerves, irrespective of arm or leg nerves, we used its presence in at least one motornerve in the arm as the criterion. For prolonged distal latency we also used presence in at least one motor nerve in the arms as a criterion instead of its presence in at least two motor nerves, irrespective of arm or leg nerves.
The reports of sural nerve biopsies were reviewed in a random order without knowledge of the patient's clinical data. Theconclusions of the neuropathologist were classified as: (1) Not consistent with CIDP
that is, either with abnormalities suggestive of another diagnosis or with no or no specific abnormalities; and (2) consistent with CIDPthat is, with demyelination or with both demyelination and cellular infiltrates.
ASSESSMENT OF THE DIAGNOSTIC BEHAVIOUR OF A NEUROLOGIST
Firstly, a neurologist experienced in diagnosis of peripheral nerve disorders (MV) reviewed the clinical data of each patient from the period before sural nerve biopsy and recorded the followingclinical diagnoses: No CIDP; CIDP with low probability; CIDP with moderate probability; CIDP with high probability; and almost definite CIDP. The within observer reliability of his diagnostic behaviour was assessed within a subsample of the patients at least two months after he had recorded the first diagnosis.
Two months after the first assessment without the results of sural nerve biopsy, the same clinical data were presented tothe same neurologist in a randomly selected order, but this time in combination with the conclusions of the biopsy reports. Again, the neurologist recorded a diagnosis as mentioned previously.
APPROACH TO GOLD STANDARD
Follow up data of all patients, consisting of clinical course after biopsy, response to treatment, and diagnosis established by the treating neurologist, were screened. The final diagnosis(1)a diagnosis other than CIDP or (2) CIDPwas based on a relapsing, remitting course after biopsy or a beneficial response to treatment with either intravenous immunoglobulin (IVIg), plasma exchange, or prednisone in patients with clinical signs and symptoms of CIDP. When these data were unequivocal, the diagnosis established by the neurologist who treated the patient was decisive.
 | Analysis |
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The patients' demographic characteristics and clinical features were analysed with descriptive statistics.
ANALYSIS OF OBJECTIVE DIAGNOSTIC VALUE OF THE CLINICAL FEATURES AND SURAL NERVE BIOPSY
For each of the six clinical features, as well as the biopsy, we calculated sensitivity (the proportion of patients with CIDPwho had a positive test result), specificity (the proportion of patients who did not have CIDP and had a negative test result), and positive likelihood ratios (LRs) for CIDP. A positive LR refers to the odds of a positive diagnostic test result in a patient with CIDP compared with a patient without CIDP.
Next, we entered the six clinical features into a logistic model to identify all significant (p
0.20) features. These significant features, as well as the conclusions of sural nerve biopsy reports were additionally forced into a second logistic model. The effectsizes of both models were expressed as odds ratios. The odds ratio approximates how much more likely (or unlikely) CIDP is among patients with the characteristic of interest than among patients without that characteristic.
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DESCRIPTION OF DEMOGRAPHIC CHARACTERISTICS OF THE PATIENTS
Sixty four patients fulfilled the inclusion criteria listed in the methods section. There were 37 males and 27 females, aged 4-80 (median 54.0) years. Onset of disease before biopsy rangedfrom one month to 11 years (median 11.5 months). The median follow up period of all patients was three months (range 0.5-67 months) after the biopsy had been taken.
DESCRIPTION OF FOLLOW UP DATA AND CONCLUSIONS OF SURAL NERVE BIOPSY REPORTS
According to the approach to the gold standard 23 patients had CIDP and 41 had another diagnosis. Nineteen of 23 patients with CIDP had a beneficial response to treatment with IVIg, plasmaexchange, or prednisone. One patient with CIDP improved spontaneously and three patients did not improve after immunomodulating treatment. These patients were diagnosed as CIDP by the treating neurologist. Table1 shows the other diagnoses.
