New research finds that small fiber neuropathy is linked with RLS and has a significant impact on quality of life.

By Lisa Spear

If neurologists don’t evaluate neuropathy patients for restless legs syndrome (RLS), some of these individuals might receive the wrong medications or not get the treatment they need, says Urvi Gautam Desai, MD, a neurologist and sleep specialist who works in North Carolina.

“We can improve the quality of life for these patients by addressing RLS symptoms and not just focusing on the neuropathic symptoms,” says Desai, an American Academy of Neurology (AAN) member.

Clinicians need to tailor patients’ medications to their underlying pathophysiology or they might do harm. For instance, selective serotonin reuptake inhibitors (SSRIs) may help some people with neuropathy but can aggravate restless legs symptoms, and potentially lead to negative outcomes.1

“A lot of times the symptoms of RLS and neuropathy, especially the small fiber neuropathy, overlap.…It is important to differentiate between the two, but it is also important to recognize that these two entities can coexist,” she says. RLS and neuropathy patients alike may talk about paresthesia as well as experiences of pain.

By asking poignant questions, providers can offer more precise care. Research is now in progress to investigate these overlapping conditions. Currently, Desai is working on a prospective study to evaluate the prevalence of RLS in small fiber neuropathy patients. Preliminary results, now published as an abstract in Neurology, show that small fiber neuropathy is associated with RLS with significant impact on quality of life.2

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According to preliminary data from the abstract, which was slated to be presented at the canceled AAN Annual Meeting, 13 patients who were diagnosed with small fiber neuropathy and showed reduced intradermal nerve fiber layer density were screened for RLS with the International RLS study group’s standardized questionnaire. All patients who answered yes to three or four questions were considered positive. The researchers went on to perform additional analysis regarding RLS severity.

All 13 patients said they experienced unpleasant sensations combined with an urge to move their legs and 90.91% noticed symptoms at rest or periods of inactivity. About 54% said these sensations improved with movement and that these feelings become worse at night or in the evening.

The researchers say that the investigation of the correlation between the severity of small fiber neuropathy and RLS severity will enhance the medical world’s understanding of these comorbidities.

Desai hopes that neurologists take away at least one message from the emerging research. She says, “Clinicians should really be looking at whether there is a coexistence of these two [comorbidities] and how can we address these symptoms.”

Lisa Spear is the associate editor of Sleep Review.


1. Hsu Y, Yang H, Huang W, Et al.  Use of antidepressants and risks of restless legs syndrome in patients with irritable bowel syndrome: A population-based cohort study. Plos One. 2019; doi.org/10.1371/journal.pone.0220641

2. Desai U, Brooks B. Prevalence of restless leg syndrome in skin biopsy proven small fiber neuropathy. Neurology Apr 2020;94(15):5243.