Definitions of the levels of the recommendations (A, B, C, U) and classification of the evidence (Class I through Class IV) are provided at the end of the "Major Recommendations" field.
Role of Clinical Autonomic Testing in the Evaluation of Polyneuropathy
Conclusions
Autonomic testing is probably useful in documenting autonomic nervous system involvement in polyneuropathy (Class II and III). The sensitivity and specificity vary with the particular test. The utilization of the combination of autonomic reflex screening tests in the composite autonomic scoring scale (CASS) probably provides the highest sensitivity and specificity for documenting autonomic dysfunction (Class II).
Recommendations
Autonomic testing should be considered in the evaluation of patients with polyneuropathy to document autonomic nervous system involvement (Level B). Autonomic testing should be considered in the evaluation of patients with suspected autonomic neuropathies (Level B) and may be considered in the evaluation of patients with suspected distal small fiber sensory polyneuropathy (SFSN) (Level C). The combination of autonomic screening tests in the CASS should be considered to achieve the highest diagnostic accuracy (Level B).
Role of Nerve Biopsy in the Evaluation of Polyneuropathy
Conclusions
There is no evidence to support or refute a conclusion regarding the role of nerve biopsy in the evaluation of distal symmetric polyneuropathy (DSP) (Class IV).
Recommendations
No recommendations can be made regarding the role of nerve biopsy in determining the etiology of DSP (Level U).
Role of Skin Biopsy in the Evaluation of Polyneuropathy
Conclusions
Intraepidermal nerve fibers (IENF) density assessment using protein-gene-product 9.5 (PGP 9.5) immunohistochemistry is a validated, reproducible marker of small fiber sensory pathology. Skin biopsy with IENF density assessment is possibly useful to identify DSP which includes SFSN in symptomatic patients with suspected polyneuropathy (Class III).
Recommendations
For symptomatic patients with suspected polyneuropathy, skin biopsy may be considered to diagnose the presence of a polyneuropathy, particularly SFSN (Level C).
Definitions:
Classification of Recommendations
The strength of practice recommendations is linked directly to the level of evidence:
Level A = Established as effective, ineffective, or harmful (or established as useful/predictive or not useful/predictive) for the given condition in the specified population. (Level A rating requires at least two consistent Class I studies.*)
Level B = Probably effective, ineffective, or harmful (or probably useful/predictive or not useful/predictive) for the given condition in the specified population. (Level B rating requires at least one Class I study or two consistent Class II studies.)
Level C = Possibly effective, ineffective, or harmful (or possibly useful/predictive or not useful/predictive) for the given condition in the specified population. (Level C rating requires at least one Class II study or two consistent Class III studies.)
Level U = Data inadequate or conflicting; given current knowledge, treatment (test, predictor) is unproven.
*In exceptional cases, one convincing Class I study may suffice for an "A" recommendation if: 1) all criteria are met, 2) the magnitude of effect is large (relative rate improved outcome > 5 and the lower limit of the confidence interval is > 2).
Classification of Evidence for Studies of Diagnostic Accuracy
Class I: A cohort study with prospective data collection of a broad spectrum of persons with the suspected condition, using an acceptable reference standard for case definition. The diagnostic test is objective or performed and interpreted without knowledge of the patient's clinical status. Study results allow calculation of measures of diagnostic accuracy.
Class II: A case control study of a broad spectrum of persons with the condition established by an acceptable reference standard compared to a broad spectrum of controls or a cohort study where a broad spectrum of persons with the suspected condition where the data was collected retrospectively. The diagnostic test is objective or performed and interpreted without knowledge of disease status. Study results allow calculation of measures of diagnostic accuracy.
Class III: A case control study or cohort study where either persons with the condition or controls are of a narrow spectrum. The condition is established by an acceptable reference standard. The reference standard and diagnostic test are objective or performed and interpreted by different observers. Study results allow calculation of measures of diagnostic accuracy.
Class IV: Studies not meeting Class I, II or III criteria including consensus, expert opinion, or a case report.
