By Alexander Shtilbans, MD, PhD 
Assistant Professor of Neurology,
Weill Cornell Medical College

Dr. Shtilbans reports no financial relationships relevant to this field of study.

SYNOPSIS: Restless legs syndrome is prevalent in patients with post-polio syndrome and is associated with decreased quality of life and fatigue.

SOURCE: Romigi A, et al. Restless legs syndrome and post polio syndrome: A case-control study. Eur J Neurol 2015;22:472-78.

Restless leg syndrome (RLS) is a sensorimotor disorder characterized by a distressing urge to move the legs and occasionally the arms, usually accompanied by an uncomfortable sensation of pain in the affected body parts, mostly the legs. The sensations occur particularly in the evening or at night and are relieved by movements. RLS can be primary or secondary due to metabolic abnormalities. The pathophysiology of primary RLS is still poorly understood, but is thought to be related, at least in part, to dysfunction of central dopaminergic system, iron metabolism, and opioid neurotransmission. Secondary RLS is classically associated with iron deficiency anemia, pregnancy, or uremia in end-stage renal disease. Post-polio syndrome (PPS) affects patients with a history of acute poliomyelitis and is characterized by worsening muscle weakness and new and progressive generalized fatigue affecting quality of life of the patients.

The authors of this paper conducted a case-control, cross-sectional study aimed to investigate the prevalence of RLS, fatigue, and daytime sleepiness in patients with PPS compared to controls.

In this trial, 78 patients with PPS and 90 control subjects matched by age and sex were screened. Exclusion criteria for both groups were secondary forms of restless leg syndrome as well as current treatment with clonazepam, dopamine agonists, antidepressant medications, or neuroleptics. The study consisted of collection of demographic data and face-to-face evaluation by a sleep neurologist who administered a questionnaire and performed a clinical examination. In particular, severity of fatigue was assessed using a fatigue severity scale, and health-related quality-of-life was evaluated by a short-form health survey. Stanford Sleepiness Scale was used to evaluate daytime sleepiness. Patients and controls were categorized into four subgroups: patients with PPS without RLS, patients with PPS and RLS, controls without RLS, and controls with RLS.

The results showed that of the 66 enrolled PPS patients, 42 (63.6%) experienced RLS symptoms. None of them had RLS prior to PPS onset. Of the 80 recruited health controls, six subjects (7.5%) were affected by RLS. Based on this, calculated odds ratio (OR) of RLS in PPS patients was 21.5, and was statistically significant. Both men and women with PPS had similar ORs for RLS. Fatigue severity scale scores were higher in PPS patients affected by RLS compared to PPS patients who didn’t have RLS. There was no significant difference in daytime sleepiness measures. Health-related quality of life scores were lower in PPS/RLS patients. The authors didn’t find any correlation between RLS rating scale and Medical Research Council strength rating scores and PPS duration.

Overall, the authors concluded that patients with PPS have high prevalence of RLS, suggesting significant comorbidity between PPS and RLS. They also hypothesized that both conditions could have a common pathological process, such as central nervous system inflammation. Alternatively, the diencephalon-spinal dopaminergic pathway could be an anatomical entity involving both RLS and PPS. The authors further suggested that PPS can be considered a possible cause of secondary form of RLS.

COMMENTARY

The authors of the current case-control study evaluated the prevalence of RLS among a group of patients with history of PPS compared to healthy controls. Besides establishing the prevalence to be 63.6%, the authors found a high correlation of fatigue and decreased quality of life with increased OR of having RLS in patients’ group. The authors argue that fatigue may be partially related to occurrence and severity of RLS. They further hypothesized that RLS could represent a possible cause for the circadian fatigue seen in PPS.

This study is one of the first to be conducted to evaluate the prevalence of RLS in PPS patients. It was well designed, but the PPS group had slightly more women compared to the control group. In addition, subjects taking clonazepam, dopamine agonists, antidepressants, or neuroleptics were excluded from the study, while the authors didn’t say anything about those taking opioids or gabapentin enacarbil extended-release, which are routinely prescribed for patients with RLS. This omission could have altered the calculated prevalence of RLS in both groups. Other limitations included a lack of population-based sampling and evaluation of other comorbidities. Nonetheless, PPS can be considered a possible cause of the secondary form of RLS.