Diagnostic value of sural nerve biopsy in chronic inflammatory demyelinating polyneuropathy

OBJECTIVE—To investigate the additional diagnosticvalue of sural nerve biopsy of 64 patients in whom chronic inflammatorydemyelinating polyneuropathy (CIDP) was considered, as sural nervebiopsy is recommended in the research criteria of an ad hocsubcommittee to diagnose CIDP.
METHODS—Firstly, the additional diagnostic valueof sural nerve biopsy was analysed with multivariate logistic re-gression. Six clinical features (remitting course, symmetricsensorimotor neuropathy in arms and legs, areflexia, raised CSF proteinconcentration, nerve conduction studies consistent with demyelination,and absence of comorbidity or relevant laboratory abnormalities) wereentered into a logistic model. Afterwards, all significant featuresidentified from this model, as well as the results of sural nervebiopsy were forced into a second logistic model. Secondly, thediagnostic performance of a neurologist experienced in diagnosis ofperipheral nerve disorders was studied by receiver operatingcharacteristics (ROC) curve analysis.
RESULTS—The results of the first logistic analysisshowed that CSF protein concentration >1 g/l (odds ratio (OR)=38.5)and neurophysiological studies consistent with demyelination (OR=51.7)were strong predictors of CIDP. When forcing the significant featuresand the sural nerve biopsy data into the model, an independentpredictive value of sural nerve biopsy could not be found. Theneurologist was able to discriminate patients with and without CIDP(area under the curve (AUC)=0.95). His diagnostic performance did notimprove significantly by offering him the results of sural nerve biopsy.
CONCLUSION—Any additional diagnostic value ofsural nerve biopsy in the diagnosis of CIDP could not be shown.

     

Ethylene oxide polyneuropathy: clinical follow-up study with morphometric and electron microscopic findings in a sural nerve biopsy

Summary A case is reported of ethylene oxide polyneuropathy after 5 months of exposure. There was symmetrical distal weakness of both lower extremities and transitory reduced nerve conduction velocities with increased latencies. Sural nerve biopsy revealed nerve fibre degeneration of the Wallerian type, associated with reduction of axonal cross-sectional areas and some degree of nerve fibre regeneration that could be confirmed morphometrically. In addition, there was conspicuous paranodal vesicular disintegration of individual myelin lamellae. Unusual cisternae with introverted hemidesmosomes were noted in endoneurial fibroblasts.Support from the Deutsche Forschungsgemeinschaft (Schr 195/5-5)     

Clinical outcome of sural nerve biopsy: a retrospective study

Sural nerve biopsy is a valuable tool in establishing the diagnosis and investigating the underlying causes of peripheral neuropathies. Few investigations have been carried out in which the sequelae of this procedure have been described systematically. We studied the short-term adverse reactions in 110 patients and the long-term outcome of sural nerve biopsy in a subgroup of 54 patients after 5–32 months. Long-lasting sensory deficits were reported in 93%, dysaesthesia in 19% and mild persistent pain in 33% of the 54 patients. No significant differences were found between patients followed for 1–2 years and those followed for more than 2 years in the frequency and distribution of hypaesthesia and anaesthesia. However, dysaesthesia was less frequent after more than 2 years (6/32 vs 1/16), and persistent pain completely subsided within our observation period. We conclude that disabling sequelae regress and finally subside over time. If we assume that returning for follow-up visits may cause bias towards more severely affected patients, the overall prognosis may be even better. Received: 12 March 1998 Received in revised form: 13 May 1998 Accepted: 10 June 1998     

Sensory conduction of the sural nerve in polyneuropathy

Using surface electrodes, sensory nerve action potentials (SAP) have been recorded in the proximal segment (mid-calf to lateral malleolus) and the distal segment (lateral malleolus to toe 5) of the sural nerve and in the median nerve in 79 control subjects. The values obtained for the distal segment of the sural nerve varied widely and in seven apparently normal subjects no SAP could be distinguished. In the proximal segment conduction velocities were over 40 m/s and there was no significant change with age, unlike the median nerve in which a highly significant slowing occurred with age. Comparison of the results of sural and median sensory conduction studies in 300 consecutive patients screened for sensory polyneuropathy confirms the value of sural nerve sensory studies as a routine screening test, and confirms the belief that the changes in polyneuropathy are usually more prominent in lower limb nerves. It is therefore suggested that studies of sural sensory conduction form the single most useful test in the diagnosis of sensory polyneuropathy.     

Sensory potentials and sural nerve biopsy: a model evaluation

Compound action potentials (CAPs) were recorded from the sural nerve prior to nerve biopsy in patients with various kinds of polyneuropathy. A previously developed volume conductor model for the CAP is applied to analyze the recorded CAPs in close relation with the morphological findings in the biopsy. First, the fiber diameter histograms obtained from the biopsy are used to simulate CAPs, by assuming a linear relation between fiber diameter and propagation velocity. It is concluded that the simulated CAPs deviate systematically from the recorded CAPs. Next, the assumption of a linear diameter-velocity relation is left, and the assumed fiber velocity distribution is adapted to obtain optimal model reconstructions of the recorded CAPs. It is concluded that the model is capable of reconstructing the recorded CAPs, including slow components and small polyphasic potentials in the case of severe fiber loss. It is demonstrated how the diameter histogram and the optimal velocity distribution can be combined to an empirical estimate of the diameter-velocity relation.     

Two-segment sural nerve conduction measurements in polyneuropathy.

Sensory conduction velocity of the sural nerve was measured in 50 normal subjects and 100 consecutive patients with suspected or established diagnosis of peripheral neuropathy. The sensory action potential was recorded by the orthodromic technique for the distal and the proximal segments. In the patient group, sensory conduction of the proximal segment appeared to be more consistent and easier to carry out as compared to the distal segment. Measurements of the latter segment alone could sometimes be misleading. Some practical points acquired from our experience with this method that allow considerable reduction of the examination time and the patients's discomfort are reported.     

Negative sural nerve biopsy in neurolymphomatosis

Patients with non-Hodgkin’s lymphoma occasionally develop widespread invasion of peripheral nerves by tumor cells or neurolymphomatosis (NL). Clinically this usually results in asymmetrical, progressive, and painful polyneuropathy. Diagnosis rests on the identification of tumor cells in peripheral nerves. To avoid false-negative biopsy findings in patients with malignant lymphomatous infiltration of peripheral nerves it has been recommended to biopsy clinically involved nerves. We present two patients with histologically confirmed NL in whom sural the nerve biopsy finding was negative despite clinical and neurophysiological evidence of involvement of the sural nerve a. The clinical features of NL are reviewed. Some patients with neurolyphomatosis have only focal or proximal involvement of nerves, requiring the biopsy of an affected part of these nerves. Magnetic resonance imaging may be useful in identifying affected nerves. Received: 28 January 1999 Received in revised form: 7 July 1999 Accepted: 17 July 1999     

Discomfort after fascicular sural nerve biopsy

Sural nerve biopsy may, in selected cases, give valuable information in the investigation of patients with polyneuropathy. The prevalence and severity of patient discomfort after fascicular nerve biopsy was investigated in 67 patients by a mailed questionnaire. A lasting (greater than 6 months) significant discomfort was found in 6 patients (11%), in 3 of these the symptoms were graded as severe. Thus, sural nerve biopsy should be limited to cases in which important information may be expected and the patients should be carefully informed of the risks of long-lasting discomfort.     

Peripheral nerve changes in porphyric neuropathy: Findings in a sural nerve biopsy

Summary The changes in a sural nerve biopsy of a patient with porphyric neuropathy were studied by light and electron microscopy. Linear arrays of myelin ovoids constituted the most common abnormality in whole mounts of teased-fiber preparations. Round or irregular formations of variable osmiophilia were the most frequent finding in thick-section preparations examined by phase contrast microscopy. Lamellar whorls represented the most prevalent lesion in thinsections studied under the electron microscope. In addition, along the teased fibers, segmental demyelination was definitely detected, although rarely; in thick sections, the true extent of the nerve fiber loss was fully appreciated; in thin sections, a variety of axon and myelin changes of a distinct character were discovered. The studies demonstrate that in peripheral nerves of porphyric neuropathy, axonand myelin changes generally run together and proceed pari passu in the same segment of nerve fiber. Furthermore, among the pathogenetic mechanisms invoked to account for the neuropathic changes none are favored to the exclusion of others by these studies. Therefore, a primary axonaland myelinic disorder on the basis of a deranged porphyrin metabolism is as good a possibility as any hitherto advanced explanation of the pathogenesis of the neuropathic changes. The secondary lesions of Wallerian degeneration and segmental demylination may simple be grafted upon the primary lesions evoked by the metabolic abnormality.     

Peripheral nerve pathological findings in familial amyloid polyneuropathy: a correlative study of proximal sciatic nerve and sural nerve lesions

To analyze the peripheral nerve pathological abnormalities in familial amyloid polyneuropathy, a correlative pathological study was carried out on the spinal nerve roots, proximal sciatic nerves, sural nerves, and brachial plexuses from 3 patients with the disease in Japan. The spinal nerve roots appeared to be unaffected except for amyloid deposition on the epineurium. In sciatic nerves and brachial plexuses the nerve lesions had a multifocal distribution, showing prominent interstitial edema in the endoneurium frequently adjacent to deposits of amyloid; in these regions the nerve fibers were severely depleted. A teased-fiber study revealed that segmental demyelination was the predominant type of nerve fiber abnormality. However, these findings were not seen in the sural nerves; instead a diffuse fiber loss with axonal degeneration was observed. It is suggested that multifocal lesions in the proximal portions of the long extremity nerves could summate distally to produce a symmetrical polyneuropathy in the disease. In addition to a space-occupying effect of amyloid deposits in the endoneurium, severe endoneurial edema associated with amyloid deposition in blood vessels and the endoneurial interstitium may induce ischemia in nerve fibers, thus causing the progressive polyneuropathy in this disorder.     

Electron microscopic observations of sural nerve in familial opticoacoustic nerve degeneration with polyneuropathy

Summary Electron microscopic data are presented on a sural nerve biopsy from a patient with familial opticoacoustic nerve degeneration with polyneuropathy. This disease is not yet defined clinically, but is similar to Charcot-Marie-Tooth disease and Refsum's disease. Examination showed a hypertrophic neuropathy with onion-bulb formations. There was often abnormal elongation or an occasional circle of the basement membrane of a Schwann cell around the core of the onion-bulb. Degeneration of the myelin sheath and the axon, very rare remyelinative changes, and non-specific lipid deposits in the Schwann cell cytoplasm were observed. Unusual inclusions in the Schwann cells or accumulations in the endoneurium were not observed. Specific findings were not found in this study. These findings were considered to be those of the early changes of a chronic neuropathy.

---

Zusammenfassung Es werden die elektronenmikroskopische Befunde der Nervenbiopsie eines Patienten mit familiärer optikoakustischer Nervendegeneration und Polyneuropathie mitgeteilt. Diese Krankheit, die noch nicht klinisch abgerenzt ist, ähnelt der Charcot-Marie-Tooth-Krankheit wie auch der Refsumschen Krankheit. Eine hypertrophische Neuropathie mit Zwiebelschalenstrukturen wurde festgestellt. Die Zwiebelschalenstruktur erscheint oft bedingt durch eine abnorme Verlängerung der Schwann-Zellbasalmembran, die manchmal den Zwiebelschalenkern ringförmig einwickelt. Es wurden auch Degeneration der Markscheide und des Achsencylinders, unbedeutende Remyelinisierungsvorgänge und unspezifische Lipoid-Ablagerungen im Cytoplasma der Schwann-Zellen beobachtet. Abnorme Einschlüsse in den Schwann-Zellen, pathologische Ablagerungen im Endoneurium wie auch andere spezifische Befunde wurden nicht festgestellt. Die Befunde wurden als Frühveränderungen einer chronischen Neuropathie interpretiert.

     

Unmyelinated fibers in sural nerve biopsies of chronic inflammatory demyelinating polyneuropathy

Summary Seven patients aged 29 to 76 years with various clinical subtypes of chronic inflammatory demyelinating polyneuropathy (CIDP) were investigated. Sural nerve biopsies were performed between 7 months and 19 years after onset of disease. Quantitative electron microscopy revealed involvement of primary unmyelinated fibers (UF) in all cases. When compared with age-matched controls from the literature and two controls of our own, there was an increase of degenerating primary UF in all cases, a definite decrease of density per mm² or number per nerve after subtraction of regenerates of myelinated and unmyelinated fibers in five cases, an increase of denervated Schwann cell complexes of the unmyelinated type in three cases, and an increased incidence of a high ratio (3) of primary UF per Schwann cell complex in five cases. Presumably due to the small number and heterogeneity of cases, the results did not correlate with type and duration of CIDP, but were obviously influenced by the degree of demyelination. The possible causes of UF damage in CIDP are discussed.     

Comparison between fascicular and whole sural nerve biopsy

Sural nerve regeneration and sensation were evaluated in 16 subjects five or more years after fascicular or whole nerve biopsy. Conduction studies demonstrated successful nerve regeneration in all subjects who had whole nerve biopsy. Postbiopsy interrogation revealed no long-term pain or paresthesias but a high incidence of tactile-induced dysesthesias. No significant difference was seen when areas of sural sensory loss were compared in fascicular and whole nerve biopsy groups. We conclude that whole nerve biopsy should be recommended in preference to fascicular biopsy since it is simpler, has greater diagnostic potential, and allows for a more complete morphological evaluation.     

Prospective study of the usefulness of sural nerve biopsy

OBJECTIVE: This study aimed to determine the usefulness of sural nerve biopsy in neurological practice. METHODS: The first prospective study of sural nerve biopsy in 50 consecutive patients was undertaken. The investigating neurologist declared the prebiopsy diagnosis and management plan and after 3 months an independent neurologist evaluated the contribution of the biopsy to diagnosis and management. An independent audit officer sought information from the patient about the adverse effects and value of the biopsy after 6 weeks and 6 months. RESULTS: In seven cases the nerve biopsy changed the diagnosis, in 35 cases the biopsy confirmed the suspected diagnosis, and in eight cases the biopsy was non-contributory. The biopsy either changed or was helpful in guiding patient management in 60%, especially those with demyelinating neuropathy and multiple mononeuropathy. Seven patients reported having had infection and 10 reported increased pain at the biopsy site 6 months later. CONCLUSION: In a consecutive series of 50 cases, sural nerve biopsy altered the diagnosis in 14%, affected management in 60%, and caused persistent increased pain at the biopsy site in 33%.     

Usefulness of sural nerve biopsy in the genomic era

The value of peripheral nerve biopsy is now sometimes questioned due to the high complication rate and the recent development of noninvasive molecular techniques for diagnosis of hereditary neuropathy. However, the disorders that can be diagnosed by genetic analysis are limited and sural nerve biopsy is still a powerful tool for making a correct diagnosis of peripheral neuropathy. Histological evaluation of the sural nerve has long focused on changes of the two major components of peripheral nerves, axons and myelin, as well as on the detection of diagnostic changes such as amyloid deposits, sarcoid tubercles, and vasculitis. In addition to these components, the sural nerve biopsy specimen contains various important cells, including perineurial cells, mast cells, endothelial cells, pericytes, and lymphocytes. Among these cells, the endothelial cells and pericytes form the blood‐nerve barrier (BNB) and investigation of these cells can reveal important information, especially in inflammatory neuropathies. To better understand the biological basis of BNB, we established rat and human immortal cell lines from the endothelial cells and pericytes of endoneurial microvessels. Characterization of these cell lines is now underway at our laboratory. These BNB cell lines should provide useful information concerning the pathophysiology of peripheral neuropathy, and we should obtain a new perspective for the investigation of nerve biopsy specimens after understanding the molecular background of the BNB.     

Ultrastructure of the sural nerve in chronic polyneuropathy associated with Adie's syndrome

Summary The sural nerve of a woman of 35 with chronic polyneuropathy and Adie's syndrome was examined by electron microscopy. Myelinated nerve fibres were absent and there was marked reduction in the number of unmyelinated fibres. Onion bulb formation was not observed. Collagen fibres occupied the intercellular spaces.     

皮肤神经活检与神经电生理以及腓肠神经活检的初步对比观察

目的 对周围神经病的患者进行皮肤神经活检、临床特点、神经电生理和腓肠神经活检的对比观察。方法 观察7例周围神经病患者，进行皮肤神经活检、腓肠神经活检、神经电生理检查，并对这些检查的一致性进行比较。结果 7例患者的神经电生理检查均提示有周围神经损害，腓肠神经活检也有不同程度的神经病变。6例皮肤神经活检同时有远近端皮肤神经的异常，且与腓肠神经活检所见病变的严重程度相一致。此6例患者的皮肤神经异常远端重于近端，符合长度依赖性周围神经病变。结论 皮肤神经活检与临床特点、神经电生理以及腓肠神经活检的结果有高度一致性；皮肤神经活检可以反映长度依赖性周围神经病变。