No abstract

Importance Peripheral neuropathy is a highly prevalent and morbid condition affecting 2–7% of the population. Patients frequently suffer from pain and are at risk of falls, ulcerations, and amputations. We aimed to review recent diagnostic and therapeutic advances in peripheral neuropathy in distal symmetric polyneuropathy, the most common subtype of peripheral neuropathy. Observations and Advances Current evidence supports limited routine laboratory testing in patients with distal symmetric polyneuropathy. Patients without a known cause should have a complete blood count, comprehensive metabolic panel, B12, serum protein electrophoresis with immunofixation, fasting glucose, and a glucose tolerance test. The presence of atypical features such as asymmetry, non-length-dependence, motor predominance, acute or subacute onset, and/or prominent autonomic involvement should prompt a consultation with a neurologist or neuromuscular specialist. Electrodiagnostic tests and magnetic resonance imaging of the neuroaxis are the main drivers of the cost of the diagnostic evaluation, but evidence supporting their use is lacking. Strong evidence supports the use of tricyclic antidepressants, serotonin and norepinephrine reuptake inhibitors, and voltage-gated calcium channel ligands in the treatment of neuropathic pain. More intensive glucose control substantially reduces the incidence of distal symmetric polyneuropathy in patients with type 1 diabetes, but does not in type 2 diabetes. Conclusions and Relevance The opportunity exists to improve guideline concordant testing in distal symmetric polyneuropathy patients. Moreover, the role of electrodiagnostic tests needs to be further defined, and interventions to reduce magnetic resonance imaging use in this population are needed. Even though several efficacious medications exist for neuropathic pain treatment, pain is still under-recognized and undertreated. New disease modifying medications are needed to prevent and treat peripheral neuropathy, particularly in type 2 diabetes.

ObjectiveTo update the 2011 American Academy of Neurology (AAN) guideline on the treatment of painful diabetic neuropathy (PDN) with a focus on topical and oral medications and medical class effects.MethodsThe authors systematically searched the literature from January 2008 to April 2020 using a structured review process to classify the evidence and develop practice recommendations using the AAN 2017 Clinical Practice Guideline Process Manual.ResultsGabapentinoids (standardized mean difference [SMD] 0.44; 95% confidence interval [CI], 0.21–0.67), serotonin-norepinephrine reuptake inhibitors (SNRIs) (SMD 0.47; 95% CI, 0.34–0.60), sodium channel blockers (SMD 0.56; 95% CI, 0.25–0.87), and SNRI/opioid dual mechanism agents (SMD 0.62; 95% CI, 0.38–0.86) all have comparable effect sizes just above or just below our cutoff for a medium effect size (SMD 0.5). Tricyclic antidepressants (TCAs) (SMD 0.95; 95% CI, 0.15–1.8) have a large effect size, but this result is tempered by a low confidence in the estimate.Recommendations SummaryClinicians should assess patients with diabetes for PDN (Level B) and those with PDN for concurrent mood and sleep disorders (Level B). In patients with PDN, clinicians should offer TCAs, SNRIs, gabapentinoids, and/or sodium channel blockers to reduce pain (Level B) and consider factors other than efficacy (Level B). Clinicians should offer patients a trial of medication from a different effective class when they do not achieve meaningful improvement or experience significant adverse effects with the initial therapeutic class (Level B) and not use opioids for the treatment of PDN (Level B).