Diagnosing restless legs syndrome (RLS) in primary care

SUMMARY

This paper represents a review of current opinion and information on the effective diagnosis of restless legs syndrome (RLS) in a primary care setting. RLS can be a distressing condition - it can cause serious sleep disturbance and has a significant impact on quality of life comparable to that of depression or type 2 diabetes. The prevalence of adults whose RLS is severe enough to warrant medical advice has been estimated to be approximately 3%, but only a small proportion of these patients currently report having been diagnosed in primary care, despite stating that they have presented to their GP. The benefits of increased understanding of the symptoms of RLS and how patients present in primary care are discussed, with emphasis on how this will help GPs more effectively diagnose and manage the patients affected. Guidelines on how to diagnose RLS in a primary care setting are given - when a patient presents with sleep disturbance, RLS should be routinely considered and, where existing, be readily diagnosed in a primary care setting on the basis of the patient's clinical history, a physical examination and with the aid of four questions based on the International RLS Study Group (IRLSSG) four essential diagnostic criteria.     

No association between plasma hepcidin levels and restless legs syndrome - results from the Danish Blood Donor Study

BackgroundRestless Legs Syndrome (RLS) is a neurological sensorimotor disorder that occurs in the evening and night, thereby often impacting quality of sleep in sufferers. The aetiology of RLS is not completely understood although iron dysregulation has been suggested as a likely pathway. The relationship between RLS and the iron regulatory protein hepcidin has not been studied in large cohorts. We aimed to assess whether an association between plasma hepcidin variation and RLS exists in a large cohort of healthy individuals.MethodsPlasma hepcidin levels were measured in 9708 Danish blood donors from the Danish Blood Donor Study all of whom correctly completed the validated Cambridge–Hopkins RLS-questionnaire for RLS assessment.ResultsA total of 466 blood donors were determined as current RLS cases in the sample (4.8%). RLS cases had a significantly higher proportion of females (56.7% vs 46.7%; P < 0.001) and were older (median age [IQR] 40.6 years vs 38.0 years; P = 0.010) than controls. RLS cases were also more frequent smokers (P = 0.004). No significant differences were found in body mass index (BMI), alcohol consumption, time of donation and donation history between cases and controls. No difference in plasma hepcidin levels was observed between RLS cases and controls (median concentration [IQR]: 10.5 ng/ml [6.3–16.4] in RLS cases vs 10.5 ng/ml [6.0–16.5] in controls). Using a logistic regression model, we found that hepcidin levels were not associated with RLS after adjusting for age, sex, alcohol consumption, smoking status, donation time and donation history (OR = 1.00 [0.99–1.02] per 1 ng/ml increase of hepcidin; P = 0.429).ConclusionOur study in Danish blood donors did not find an association between RLS and plasma hepcidin levels. Our findings suggest that plasma hepcidin's role as a potential diagnostic biomarker of RLS is inadequate.     

Diagnosis and prognostic value of restrictive ventilatory disorders in the elderly: a systematic review of the literature

Although less extensively studied compared to pulmonary obstructive diseases, restrictive lung disease (RLD) is highly prevalent and frequently disabling in the adult and, more, the elderly population. The underlying conditions may be either primarily pulmonary diseases, such as idiopathic pulmonary fibrosis, or non respiratory conditions secondarily affecting the lung, e. g. congestive heart failure, or else conditions affecting the lung expansion, e. g. obesity or rib cage deformity. The diagnosis is frequently based on the measurement of surrogate indexes such as the forced vital capacity (FVC) used as a proxy for total lung capacity (TLC). As a consequence, diagnosis of RLD is often characterized by poor specificity. In the elderly, worsening in the quality of life and poor prognosis are variably, but significantly, associated to RLD, being the underlying condition an important source of variability. Several causes of RLD are preventable and treatable conditions. A prompt identification of these conditions may allow to slow the decline of respiratory reserve and, thus, to preserve both personal independence and resistance to acute respiratory infections. This review gives an update on the latest evidence available on the prevalence and the prognosis of RLD in the elderly. Studies were identified through systematic searches of the electronic database MEDLINE. Reference list of eligible papers were also manually searched.     

Thalamic Deep Brain Stimulation May Improve Restless Legs Syndrome in Patients With Essential Tremor

ObjectivesTo determine change in restless legs syndrome (RLS) symptoms in essential tremor (ET) patients undergoing bilateral thalamic ventral intermedius (VIM) deep brain stimulation (DBS) surgery.Materials and MethodsWe retrospectively reviewed our database of ET patients with RLS who had undergone VIM DBS for tremor from 2012 to 2020. We reviewed the patients with available International Restless Leg Syndrome Study Group RLS scale scores before and after DBS. Percentage of responders, defined as proportion of patients experiencing three or more point improvement of RLS scores post-DBS, was calculated. We performed two-tailed t-test of pre-DBS and post-DBS RLS scores.ResultsWe identified 13 patients with ET and RLS who had undergone bilateral VIM DBS, of whom nine (69%) were responders post-DBS. Five of 13 patients (38%) had complete resolution of RLS post-DBS. For all patients, mean pre-DBS RLS score was 15.8 ± 7.9 which improved by 46% post-DBS to a mean of 8.5 ± 8.8 (p = 0.007). Four patients rated their RLS scale one night with the stimulator OFF and another night with the stimulator ON. The mean RLS score with stimulator ON was 15.5 ± 7.6 which improved by 53% to a mean of 6.25 ± 7.8 (p = 0.008), with two having complete resolution of RLS with stimulator ON. Of the nine responders, six preferred to keep their stimulator ON at night due to relief of RLS and better subjective quality of sleep.ConclusionsWe report for the first time improvement of RLS in patients with ET after bilateral thalamic DBS. Although many ET patients with nonrechargeable DBS systems switch off their stimulator at night to conserve battery life, those with RLS may potentially benefit from keeping their stimulator ON at night to relieve their RLS.     

Evaluation of magnetic resonance imaging characteristics of new nitroxyl radicals on the model of RLS lymphoma

Toxic and magnetic resonance contrast characteristics of new nitroxyl radicals Fur-135 and Fur-176 were studied in experiments on mice. The test compounds exhibited low toxicity and allowed us to increase contrasting of transplanted RLS lymphoma. Fur-135 differs by the type of contrasting from Gd³⁺-containing preparation omniscan and locates the tumor focus with high precision. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 143, No. 2, pp. 202–205, February, 2007     

Functional connectivity alternation of the thalamus in restless legs syndrome patients during the asymptomatic period: a resting-state connectivity study using functional magnetic resonance imaging

BackgroundRestless legs syndrome (RLS) is a primary sensory disorder with a secondary motor component (e.g., urge to move), and the thalamus is known to play a central role in RLS. The purpose of our study was to explore the intrinsic changes in the thalamocortical circuit in RLS patients using a resting-state functional magnetic resonance imaging (fMRI) paradigm.MethodsResting-state fMRIs were obtained in the morning from 25 idiopathic RLS patients who were not using RLS medications and 25 controls. Resting-state connectivity was analyzed by a seed-based method using Analysis of Functional NeuroImages (AFNI) software with the bilateral thalami (ventroposterolateral nucleus [VPLN]). The connectivity characteristics of RLS patients were compared to those of the controls.ResultsWe found that RLS patients showed reduced thalamic connectivity with the right parahippocampal gyrus, right precuneus, right precentral gyrus, and bilateral lingual gyri; however, the right superior temporal gyrus, bilateral middle temporal gyrus, and right medial frontal gyrus showed enhanced connectivity with the thalamus. RLS severity was negatively correlated with connectivity between the thalamus and right parahippocampal gyrus (r = −0.414; P = .040).ConclusionsOur results suggest that the characteristics of the connectivity changes may reflect the pathways involved in producing RLS symptoms and indicate that RLS patients may have deficits in controlling and managing sensory information, which supports the act of viewing RLS as a disorder disrupting somatosensory processing.     

Electrophysiological pattern of involuntary limb movements in the restless legs syndrome

Patients with restless legs syndrome (RLS) suffer from involuntary limb movements during the day. We studied these leg movements in 18 idiopathic (n = 8) and uremic (n = 10) patients at rest. Electromyographically measured muscle contractions were preceded by sensory discomfort in all patients. The mean duration of the contractions ranged between 0.67 and 5.71 s with a mean frequency of 244 epochs of muscle activity per hour. Seven of 18 patients showed a constant order of recruitment with propagation of muscle activity up or down spinal segments (L3 to S1 and vice versa). No difference in electrophysiologically recorded patterns was observed between patients with idiopathic and uremic RLS. We suggest a brainstem disinhibition phenomenon as the pathological mechanism that activates a spinal generator. The spinal origin of the involuntary limb movements in patients with RLS is confirmed by the long duration of jerks, the recruitment characteristics, and the periodicity of the jerks. No jerk could be elicited by sensory reflexes. © 1996 John Wiley & Sons, Inc.     

Iron-deficiency and dopaminergic treatment effects on RLS-Like behaviors of an animal model with the brain iron deficiency pattern of the restless legs syndrome

BackgroundBrain iron deficiency (BID), especially for the substantia nigra (SN), without peripheral iron deficiency (ID) has been well documented as a ubiquitous finding for restless legs syndrome (RLS) patients. This close association suggests the biology of RLS BID can produce RLS symptoms. Association, however, cannot establish such a direct relationship. Instead, the BID of RLS could be experimentally produced to determine if it then produces significant RLS-like biological or behavioral features. Forward genetics approach led to identification from the BXD strains the BXD40 females (BXD40f) as a putative animal model for the RLS BID. The BXD40f on an iron-sufficient diet have a lower iron in the VMB (containing the SN) during the active but not inactive period. This was not found for the other BXD strains evaluated. The BXD40f on an ID diet uniquely have even greater reduced VMB but not peripheral iron, matching the RLS BID pathophysiology. A prior report found that the BXD40f on an iron-sufficient diet had an RLS-like behavior of increased activity occurring only in the last part of the active period that was not present in the other strains without the low VMB iron. This increased activity matches the circadian pattern of symptoms in RLS patients with increased urge or drive to move in the last part of the day. This study asks first: if you decrease the VMB iron by an iron deficient diet do the RLS-like behaviors worsen; and second will the dopaminergic treatments effective for RLS also reduce the worsened RLSlike behaviors.MethodsIn sum, 13 BXD40f mice post weaning were randomly assigned for 100 days to either a iron-sufficient diet (n = 6) or an ID diet (N = 7). They were then evaluated for 24-h activity in their home cage using implanted G2 EMitter telemetry device. At 3 h before the end of the active period IP doses were given every other day of either: saline (vehicle only), 12.5 mg levodopa, 25 mg levodopa, 0.5 mg quinpirole, or 1 0.0 mg quinpirole.ResultsThe ID compared to irons-sufficient diet produced earlier onset of the RLS-like behavior matching the earlier onset of symptoms with increasing severity of RLS. The dopaminergic treatments significantly reduced the RLS-like behavior. Added analyses of the RLS-like behaviors as decreased resting times showed similar results to activity increases.ConclusionsThese data demonstrate both that The BXD40f provide a useful animal model of RLS and also strongly support the hypothesis that the biology of RLS BID can produce RLS symptoms.