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 Laboratory Testing in the Evaluation of Polyneuropathy
Conclusions
Screening laboratory tests are possibly useful in determining the cause of distal symmetric polyneuropathy (DSP), but the yield varies depending upon the particular test (Class III). The tests with the highest yield of abnormality are blood glucose, serum B12 with metabolites (methylmalonic acid with or without homocysteine), and serum protein immunofixation electrophoresis (Class III). Patients with distal symmetric sensory polyneuropathy have a relatively high prevalence of diabetes or prediabetes (impaired glucose tolerance), which can be documented by blood glucose or glucose tolerance testing (GTT) (Class III).
Recommendations
Screening laboratory tests may be considered for all patients with DSP (Level C). Although routine screening with a panel of basic tests is often performed (see table e-1 in the original guideline document), those tests with the highest yield of abnormality are blood glucose, serum B12 with metabolites (methylmalonic acid with or without homocysteine), and serum protein immunofixation electrophoresis (Level C). When routine blood glucose testing is not clearly abnormal, other tests for prediabetes (impaired glucose tolerance) such as a GTT may be considered in patients with distal symmetric sensory polyneuropathy, especially if it is accompanied by pain (Level C).
Although there are no control studies (Level U) regarding when to recommend the use of other specific laboratory tests, clinical judgment correlated with the clinical picture will determine which additional laboratory investigations (see table e-2 in the original guideline document) are necessary.
Role of Genetic Testing in the Evaluation of Polyneuropathy
Conclusions
Genetic testing is established as useful for the accurate diagnosis and classification of hereditary polyneuropathies (Class I). For patients with a cryptogenic polyneuropathy who exhibit a classic hereditary neuropathy phenotype, routine genetic screening may be useful for Charcot-Marie-Tooth 1A (CMT1A) duplication/ deletion and Cx32 mutations in the appropriate phenotype (Class III). Further genetic testing may be considered guided by the clinical question. There is insufficient evidence to determine the usefulness of routine genetic screening in cryptogenic polyneuropathy patients without a classic hereditary neuropathy phenotype.
Recommendations
Genetic testing should be conducted for the accurate diagnosis and classification of hereditary neuropathies (Level A). Genetic testing may be considered in patients with a cryptogenic polyneuropathy and classic hereditary neuropathy phenotype (Level C). There is insufficient evidence to support or refute the usefulness of routine genetic testing in cryptogenic polyneuropathy patients without a classic hereditary phenotype (Level U).
Clinical Context
To achieve the highest yield, the genetic testing profile should be guided by the clinical phenotype, inheritance pattern (if available), and electrodiagnostic (EDX) features (demyelinating vs. axonal). See the figure in the original guideline document for guidance.
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.
