Rheumatologic serologies in secondary restless legs syndrome.

Diagnostic criteria for restless legs syndrome (RLS) have been established; however, the pathophysiology of this common condition remains elusive. Several secondary forms of RLS potentially include renal failure, iron deficiency, pregnancy, and neuropathy. RLS has also been reported in approximately 25% of patients diagnosed with rheumatoid arthritis and Sj?gren's syndrome. We performed clinical and serologic evaluations on 68 patients diagnosed with RLS to determine how many may have concurrent rheumatologic disease that could be causing their RLS symptoms. We compared these with other postulated secondary causes of RLS. No patient had clinical evidence of rheumatologic disease, and only four had any positive serologic evaluations (two positive SSA/SSB and two mildly elevated RF titers). Three of these had a positive family history for RLS. Patients without a family history of RLS did have lower ferritin levels, more cases of neuropathy, and an older age at symptom onset. We do not think rheumatologic disease represents a significant secondary cause of RLS and do not recommend serologic investigation unless there are overt clinical signs. In contrast, our study suggests that neuropathy and serum iron deficiency do represent secondary forms of RLS.     

Restless legs syndrome in diabetic neuropathy: a frequent manifestation of small fiber neuropathy

As the occurrence of restless legs syndrome (RLS) in diabetes is controversial, the aim of this study was to assess the prevalence of RLS in a cohort of patients with diabetic neuropathy and to analyze the features of the associated neuropathy. We investigated the occurrence of RLS diagnosed in accordance with the criteria of the International Restless Legs Syndrome Study Group in a cohort of patients with polyneuropathy and mononeuropathy multiplex associated with diabetes mellitus (DM), or impaired glucose tolerance (IGT), or impaired fasting glucose (IFG) in a retrospective study. RLS was present in 33/99 patients with neuropathy associated with DM/IGT/IFG (84 with distal polyneuropathy and 15 with multiple mononeuropathy). Comparing patients with or without RLS, small fiber sensory neuropathy was more common in the RLS patients (15/33 vs. 15/66), as were symptoms of burning feet (10/33 vs. 6/66). In several patients, RLS was responsive to neuropathic pain medications. The frequent occurrence of RLS in association with thermal dysesthesias may reflect the involvement of small sensory fibers in the form of hyperexcitable C fibers or A-delta fiber deafferentation. We suggest that RLS may be triggered by abnormal sensory inputs from small fibers, especially involved in neuropathy associated with DM/IGT/IFG. Our data show that RLS is a relevant feature of diabetic neuropathy, as a frequent and potentially treatable manifestation of small fiber involvement in the course of DM and IGT/IFG.     

Restless-legs syndrome

Restless-legs syndrome (RLS) is a sensorimotor disorder, characterized by an irresistible urge to move the legs usually accompanied or caused by uncomfortable and unpleasant sensations. It begins or worsens during periods of rest or inactivity, is partially or totally relieved by movements and is exacerbated or occurs at night and in the evening. RLS sufferers represent 2 to 3% of the general population in Western countries. Supportive criteria include a family history, the presence of periodic-leg movements (PLM) when awake or asleep and a positive response to dopaminergic treatment. The RLS phenotypes include an early onset form, usually idiopathic with a familial history and a late onset form, usually secondary to peripheral neuropathy. Recently, an atypical RLS phenotype without PLM and l-DOPA resistant has been characterized. RLS can occur in childhood and should be distinguished from attention deficit/hyperactivity disorder, growing pains and sleep complaints in childhood. RLS should be included in the diagnosis of all patients consulting for sleep complaints or discomfort in the lower limbs. It should be differentiated from akathisia, that is, an urge to move the whole body without uncomfortable sensations. Polysomnographic studies and the suggested immobilization test can detect PLM. Furthermore, an l-DOPA challenge has recently been validated to support the diagnosis of RLS. RLS may cause severe-sleep disturbances, poor quality of life, depressive and anxious symptoms and may be a risk factor for cardiovascular disease. In most cases, RLS is idiopathic. It may also be secondary to iron deficiency, end-stage renal disease, pregnancy, peripheral neuropathy and drugs, such as antipsychotics and antidepressants. The small-fiber neuropathy can mimic RLS or even trigger it. RLS is associated with many neurological and sleep disorders including Parkinson's disease, but does not predispose to these diseases. The pathophysiology of RLS includes an altered brain-iron metabolism, a dopaminergic dysfunction, a probable role of pain control systems and a genetic susceptibility with nine loci and three polymorphisms in genes serving developmental functions. RLS treatment begins with the elimination of triggering factors and iron supplementation when deficient. Mild or intermittent RLS is usually treated with low doses of l-DOPA or codeine; the first-line treatment for moderate to severe RLS is dopaminergic agonists (pramipexole, ropinirole, rotigotine). In severe, refractory or neuropathy-associated RLS, antiepileptic (gabapentin, pregabalin) or opioid (oxycodone, tramadol) drugs can be used.     

Restless leg syndrome in the differential diagnosis of entrapment and peripheral neuropathies

Restless leg syndrome (RLS) is an abnormal sensation disorder. Defining the syndrome is difficult. It is transmitted autosomal dominant genetically, is especially prevalent in the lower limbs, and is seen in both genders. In the differential diagnosis of RLS, nocturnal leg cramps, akathisia, peripheral neuropathy, entrapment neuropathy, and vascular disease (for example, deep vein thrombosis) should be considered. A 52-year-old woman was admitted to our clinic with signs of paresthesia, she had abnormal sensation disorder in both legs and the right arm, which she had difficulty defining. She had applied to another center with the same complaints and had been evaluated as entrapment neuropathy, carpal tunnel syndrome, and/or peripheral neuropathy. Her electromyographic examination carried out by us was normal. The history, neurological examination findings, and results of standard laboratory analyses provided a diagnosis of idiopathic RLS. After the diagnosis of RLS in the proband, we questioned other family members. Her large family had 63 members, 35 males, and 28 females. Of 63 members, 17 also had an RLS diagnosis.     

Signs of sympathetic and endothelial cell activation in the skin of patients with restless legs syndrome

ObjectivesTo evaluate skin biopsies of patients with early- and late onset restless legs syndrome (RLS) for concomitant small fiber neuropathy (SFN) and to determine cutaneous sympathetic innervation and microvascularization in comparison to healthy individuals.MethodsDensity of intraepidermal nerve fibers (IENFD), adrenergic nerve fibers and dermal capillaries was analyzed by immunofluorescence for PGP9.5, tyrosine hydroxylase and endothelial markers CD31 and CD105 in skin biopsies of 11 individuals with RLS and 8 age- and sex-matched controls.ResultsIENFD did not differ between RLS and controls, but two RLS patients with comorbid impaired glucose metabolism fulfilled morphometric criteria of SFN according to published normative values. In contrast, dermal nerve bundles of RLS patients showed an increased density of tyrosine hydroxylase⁺ adrenergic nerve fibers (p < 0.005). Moreover, an increased ratio between immature CD105⁺ and mature CD31⁺ endothelial cells within dermal capillaries was observed in RLS (p < 0.02).ConclusionsSFN, as a potential contributing factor for RLS, should be considered in patients with predisposing comorbidities presenting with burning or shooting pain, dysesthesias and impaired sensory and temperature perception. Evidence of an increased adrenergic innervation of the skin in RLS patients is in accordance with sympathetic hyperactivity while signs of endothelial cell activation may reflect an adaptive response to tissue hypoxia.     

Family recurrence and oligo-anuria predict uremic restless legs syndrome

Pizza F, Persici E, La Manna G, Campieri C, Plazzi G, Carretta E, Cappuccilli ML, Ferri B, Stefoni S, Montagna P. Family recurrence and oligo‐anuria predict uremic restless legs syndrome.
Acta Neurol Scand: 2012: 125: 403–409.
© 2011 John Wiley & Sons A/S. Objectives – To determine clinical and laboratory predictors of restless legs syndrome (RLS) in patients with end‐stage kidney disease (ESKD) undergoing long‐term hemodialysis (HD). Materials and Methods – One hundred and sixty‐two consecutive patients were assessed. History of sleep disturbances, neurological examination, clinical, and laboratory data were collected. Patients with and without RLS were compared, and a logistic regression model described the relations between independent predictors and RLS. Results – Fifty‐one patients (32%) currently had RLS (RLS+). RLS+ vs RLS? patients were more frequently women (49% vs 29%, P = 0.012), had first‐degree relative with RLS (22% vs 6%, P = 0.004), insomnia (59% vs 36%, P = 0.007), peripheral neuropathy (41% vs 21%, P = 0.006), and low residual diuresis (92% vs 68% with below 500 ml/24 h, P = 0.001). Low (OR = 8.71, CI = 2.27–33.41; P = 0.002) and absent (OR = 4.96, CI = 1.52–16.20; P = 0.008) residual diuresis, peripheral neuropathy (OR = 4.00, CI = 1.44–11.14; P = 0.008), and first‐degree relative with RLS (OR = 3.82, CI = 1.21–12.13; P = 0.023) significantly predicted RLS in ESKD patients undergoing HD. Conclusion – Positive family history for RLS together with reduced/absent residual renal function and peripheral neuropathy predicts the risk for RLS in ESKD patients undergoing HD. Longitudinal studies are warranted to correlate RLS occurrence with genetic and environmental factors.     

Association between restless legs syndrome and essential tremor.

After observing that several families with essential tremor (ET) clinically cosegregated with restless legs syndrome (RLS), we prospectively evaluated for the presence of RLS in 100 patients presenting to the Baylor College of Medicine with ET and prospectively examined all patients presenting with RLS for the presence of tremor during the same time frame. Of 100 consecutive ET patients (60 women and 75 with a family history of ET) seen over 19 weeks (current age, 65.2 +/- 16.3 years; age at tremor onset, 37.8 +/- 19.9 years) 33 met all criteria for RLS, of which 25 had never been diagnosed previously. A family history of RLS was reported in 57.6% of these 33 patients and was the only significant predictor of RLS in the ET population. Their International Restless Legs Syndrome Rating Scale score was 16.6 +/- 8.1. Over 19 weeks, we also examined 68 consecutive RLS patients (63.2% women and 54.4% with a family history of RLS) for the presence of tremor. Their current age was 55.8 +/- 14.4 years, and age at RLS onset was 33.7 +/- 19.5 years. Overtly pathological tremor was rare, but trace tremor was very common. Overall, we found a very high rate of undiagnosed RLS in patients presenting for tremor, but unlike other "secondary" forms of RLS, this finding was also associated with a high familial history of RLS, suggesting that they share some genetic similarities.     

Exploring the relationship between Parkinson disease and restless legs syndrome

BACKGROUND: Restless legs syndrome (RLS) and Parkinson disease (PD) are common neurological conditions that respond to dopaminergic therapy. To our knowledge, the relationship between the two has not been thoroughly explored. METHODS: We consecutively queried 303 patients with PD seen in our clinic for the presence of RLS symptoms, and evaluated their condition with the Epworth Sleepiness Scale and other demographic and sleep measures. We then looked for predictors of RLS in these patients with PD. We also compared a larger group of patients with PD/RLS with a group of patients with RLS alone. RESULTS: Of 303 patients with PD, 63 (20.8%) had symptoms of RLS. Neither PD patient demographics nor PD treatments could reliably predict the development of RLS symptoms; however, lower serum ferritin levels were associated with RLS symptoms in our patients with PD (P =.01). In 54 (68%) of the 79 total patients with PD/RLS (including additional patients with PD/RLS seen in the clinic) with reliable age-at-onset data, the PD symptoms preceded the RLS symptoms (chi(2) test, P<.001). Compared with patients with idiopathic RLS (N = 146), patients with PD/RLS (N = 109) were older at RLS onset (P<.001), were less likely to have a family history of RLS (P<.001), and had lower serum ferritin levels (P =.01). CONCLUSIONS: Symptoms of RLS are common in patients with PD; however, except in patients with a family history of RLS, they seem to reflect a secondary phenomenon, perhaps in relation with lower ferritin levels. There is no evidence that RLS symptoms early in life predispose to the subsequent development of PD.     

Restless legs syndrome is frequently overlooked in patients being evaluated for polyneuropathies

Restless legs syndrome (RLS) often presents with paresthesias and dysesthesisas. We have investigated the prevalence and clinical features of RLS in a cohort of patients referred for clinical suspicion of peripheral neuropathy (PN). Sixty-four patients with sensory symptoms, and 101 age-matched controls were prospectively evaluated for RLS, PN and causes of both conditions. In the 64 patients (60 ± 14 years), none were referred with a suspicion of RLS. Forty-one had a sensori-motor PN of which 22 had a definite RLS (54%). When excluding other causes of RLS, 8 of 41 patients had a RLS associated with a neuropathy (20%). The proportion of RLS in the healthy controls was 10%, lower than in the cohort of patients. In patients without PN, 57% had a RLS, and 55% in the whole cohort, a higher proportion than in the healthy controls ( P  < 0.0001). Patients with PN and RLS had more sleep disorders ( P  < 0.04), and legs and calves symptoms ( P  = 0.09) than patients with PN without RLS. Toes symptoms were more frequently observed in patients with PN but without RLS ( P  < 0.02). We conclude that RLS frequently presents with symptoms suggestive of peripheral neuropathy, and therefore, is often overlooked.     

Prevalence and clinical characteristics of restless legs syndrome in diabetic peripheral neuropathy: comparison with chronic osteoarthritis

BackgroundThe prevalence of restless legs syndrome (RLS) in patients with peripheral neuropathy has been reported to be higher than that of the general population in some studies, which suggests an association between neuropathy and RLS, but not all studies show increased RLS with neuropathy. These differences may reflect adequacy of the diagnosis, effects of chronic pain complicating the diagnosis, or population differences. Moreover, if there is increased risk for RLS with neuropathy, it may reflect consequences of the chronic pain rather than other aspects of diabetes mellitus (DM). Therefore, we investigated the effects of diagnosis rigor on the estimated prevalence of RLS in patients with diabetic peripheral neuropathy (DPN) and those with chronic leg pain from osteoarthritis (OA), and then we compared the RLS prevalence in these two populations with each other and with population prevalence for Korea.MethodsOur study is a prospective case-control study of 199 patients with DPN and 220 patients with OA. After evaluating the presence of RLS in these subjects using the diagnostic criteria of the International RLS Study Group, we confirmed the diagnosis of RLS through face-to-face interviews using the 18-item Hopkins Diagnostic Questionnaire, which removes RLS mimics; and through independent examinations by two neurologists.ResultsOf the 199 subjects with DPN, 44 (22%) appeared to have RLS from their answers on the 4-item RLS diagnostic questionnaire compared to 8 (3.6%) of 220 subjects with OA. However, the prevalence of RLS in the DPN group dropped to 16 (8%) subjects but stayed at 8 (3.6%) OA subjects when using the Hopkins Telephone Diagnostic Interview (HTDI) adapted for clinical interview. The RLS prevalence determined by HTDI remained significantly higher (P = .042) in the DPN group compared to the OA group and was twice that reported for the general Korean population (8% vs 3.9%). Among subjects with DPN, those with RLS were older (68.06 ± 8.43 years vs 62.46 ± 11.05 years; P = .049) and had higher pain scores (visual analog scale [VAS], 4.69 ± 2.52 vs 2.72 ± 2.12; P = .002). The quality of sleep (MOS [Medical Outcomes Study] sleep scale) and health-related quality of life (QoL) (total score on the 36-Item Short-Form Health Survey [SF-36]) showed no significant difference between the two groups.ConclusionsThe prevalence of RLS in patients with DPN cannot be accurately assessed with only the four diagnostic criteria interview, but the prevalence was higher than expected for Koreans from the general population prevalence and also was higher than occurred with OA patients with chronic leg pains when accurately assessed with a structured interview. Chronic leg pain from OA does not significantly complicate RLS diagnosis, and chronic pain itself does not explain the increased RLS prevalence in diabetic neuropathy.     

Cervical dystonia following peripheral trauma

Abstract. Post-traumatic cervical dystonia as a diagnostic entity remains a subject of debate. Patients with cervical dystonia (CD) were asked to identify any significant illness prior to the onset of their CD. Sixteen patients of 95 respondents reported a history of injury in the four-week period prior to onset of their dystonia. A retrospective study of the clinical characteristics of the 16 patients with early post-traumatic CD (CD-PT) in comparison with the 52 patients reporting no antecedent trauma (CD-NT) was performed. In this comparison the CD-PT group had a significantly increased frequency of laterocollis, significantly more reported pain and more reported depression. Non-significant trends were noted for less responsiveness to botulinum toxin and less use of gestes antagonistes in the CD-PT group. There were no group differences in the presence of a family history of dystonia. Eleven of the CD-PT group had been or were currently involved in litigation. A sub-group of seven CD-PT patients had laterocollis, six of whom conformed to a clinical pattern of persistent non-spasmodic laterocollis with marked pain; all seven had been involved in litigation. This form of CD-PT is a distinct clinical entity and has an onset within hours or a few days of the trauma. In contrast, no significant differences were noted between patients with CD-NT and the eight patients with later onset of CD between 4 weeks and one year after peripheral trauma.     

Prevalence of Restless Legs Syndrome in a Georgian Primary Healthcare Setting: A Pilot Study

Background: The prevalence of restless legs syndrome (RLS) is approximately 10% in Western Europe, but unknown in Georgia. This pilot study aimed to assess RLS prevalence in a focused Georgian population. Methods: An RLS epidemiological questionnaire [Allen et al.: Sleep Med 2003;4:101-119] was filled out by patients in five primary healthcare centers in two Georgian cities between March and September 2006. Additionally, questions related to RLS symptom onset, family history, treatment, sleep disturbance and history of iron deficiency were included. RLS diagnosis was based on an expert interview and an epidemiological questionnaire for RLS. Results: The total number of respondents was 115 (75% women/25% men); mean age was 47 years (range 18-85). Thirteen subjects (11.3%) reported RLS symptoms (9 women/4 men); mean age was 52 years (range 32-83). Eleven (85%) had a positive family history of RLS. All subjects had sleep disturbance and none had a history of known iron deficiency. Conclusion: The prevalence of RLS in a focused Georgian population is in line with other RLS epidemiologic studies performed in clinical settings. However, the prevalence rate of RLS in a studied group might not be representative for the general Georgian population. Further population-based epidemiological studies are required.     

Restless legs syndrome in hemodialysis patients in India: a case controlled study

OBJECTIVE: To assess the prevalence of restless legs syndrome (RLS) in Indian patients on hemodialysis as compared to controls. METHODS: One hundred and twenty-one consecutive hemodialysis patients and 99 controls were evaluated using a standard predesigned questionnaire. The control group comprised completely normal healthy adults who were being evaluated as renal donors. Nerve conduction studies were done in those patients diagnosed with RLS. RESULTS: RLS was present in eight hemodialysis patients (6.6%) and none of the controls. Patients (87.5%) with RLS had delayed sleep onset. Nerve conduction showed evidence of sensori-motor neuropathy in five patients and a normal study in one patient. When we compared the patients with RLS to those without RLS, there was no significant difference in their age, duration of hemodialysis, hemoglobin, blood urea, creatinine, serum ferritin or use of erythropoeitin. CONCLUSIONS: The prevalence of RLS was 6.6% in patients on hemodialysis; and 0% in controls, which is much lower than that reported from the West.     

SNCA-Rep1 polymorphism correlates with susceptibility and iron deficiency in restless legs syndrome

BackgroundBrain iron disequilibrium and dopaminergic dysfunction are key pathophysiological features of Restless Legs Syndrome (RLS). Rep1 polymorphism in the promotor region of SNCA is associated with risk of Parkinson's disease, however its association with RLS and iron status is unclear.ObjectiveTo investigate SNCA-Rep1 polymorphism in RLS and its phenotypes.MethodsWe recruited RLS patients as well as age and gender matched healthy controls. Demographic information and clinical features of RLS were recorded. Laboratory examinations were performed to exclude possible secondary causes.Results215 RLS patients and 369 healthy controls were included. We found that the Rep1 allele 0 homozygosity significantly decreased RLS risk (OR: 0.345; P < 0.0001, and remained significant after the Bonferroni correction). Phenotypic analysis demonstrated that longer Rep1 alleles were associated with increased susceptibility to iron deficiency (53.0% vs 36.1%, P = 0.017), however had no phenotypic significant effects on age, gender, onset age, duration, RLS family history, severity, laterality, extra body involvement and seasonal fluctuation. Multivariate logistic regression analyses confirmed long Rep1 allele was associated with higher risk of iron deficiency in RLS after adjusting for potential confounding factors. In detail, Rep1 allele 2 homozygosity was prone to a higher risk of peripheral iron deficiency in RLS (OR: 4.550, P = 0.006, remained significant after the Bonferroni correction).ConclusionThe SNCA-Rep1 variability modified RLS risk and influenced peripheral iron deficiency in this group of Chinese RLS patients. Rep1 allele 0 homozygosity decreased the risk of RLS, while homozygous allele 2 increased the risk of nonanemic iron deficiency in RLS.     

Exome Sequencing Reveals a Novel PRPS1 Mutation in a Family with CMTX5 without Optic Atrophy

Background

X-linked Charcot-Marie-Tooth disease type 5 (CMTX5) is caused by mutations in the gene encoding phosphoribosyl pyrophosphate synthetase I (PRPS1). There has been only one case report of CMTX5 patients. The aim of this study was to identify the causative gene in a family with CMTX with peripheral neuropathy and deafness.

Case Report

A Korean family with X-linked recessive CMT was enrolled. The age at the onset of hearing loss of the male proband was 5 months, and that of steppage gait was 6 years; he underwent cochlear surgery at the age of 12 years. In contrast to what was reported for the first patients with CMTX5, this patient did not exhibit optic atrophy. Furthermore, there was no cognitive impairment, respiratory dysfunction, or visual disturbance. Assessment of his family history revealed two male relatives with very similar clinical manifestations. Electrophysiological evaluations disclosed sensorineural hearing loss and peripheral neuropathy. Whole-exome sequencing identified a novel p.Ala121Gly (c.362C>G) PRPS1 mutation as the underlying genetic cause of the clinical phenotype.

Conclusions

A novel mutation of PRPS1 was identified in a CMTX5 family in which the proband had a phenotype of peripheral neuropathy with early-onset hearing loss, but no optic atrophy. The findings of this study will expand the clinical spectrum of X-linked recessive CMT and will be useful for the molecular diagnosis of clinically heterogeneous peripheral neuropathies.     

Detection of hereditary neuropathy with liability to pressure palsies among patients with acute painless mononeuropathy or plexopathy

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant disorder characterized by recurrent mononeuropathies or brachial plexopathies, commonly associated with a chromosome 17p11.2-12 deletion encompassing the peripheral myelin protein-22 (PMP22) gene. We tried to identify criteria distinguishing HNPP among patients with acute painless mononeuropathy/plexopathy. We investigated by pulsed-field gel electrophoresis the presence of the deletion in 27 patients with isolated or recurrent acute painless mononeuropathy or brachial plexopathy, and no obvious cause of neuropathy. Eight patients carried the deletion, whereas 19 had neither the deletion nor mutations in the PMP22 gene. Age at onset, presenting modality, precipitating events, and rate of recovery did not significantly differ in the two groups. Family history was informative for HNPP diagnosis in 3 cases only. HNPP patients more often showed recurrent episodes, brachial plexopathy, and clinical or electrophysiologic involvement of other nerves. Non-HNPP patients more frequently had peroneal palsy, recent weight loss, and normal electrophysiologic examination in other nerves. Signs of generalized neuropathy and evidence of disease in other family member are often subtle in HNPP and must be thoroughly investigated in patients with acute painless mononeuropathy/plexopathy. © 1998 John Wiley & Sons, Inc. Muscle Nerve 21: 1686–1691, 1998.     

Restless legs syndrome in a patient with multifocal motor neuropathy

Restless legs syndrome (RLS) has been frequently reported in association with peripheral neuropathy, and it is especially frequent in some forms of polyneuropathy with preferential involvement of small sensory fibers. Here, we describe a patient with multifocal motor neuropathy, who developed RLS during the course of the disease. Our findings support the notion that RLS may develop in the context of immune-mediated neuropathies and it should be specifically investigated even in those patients with preferentially or exclusive motor involvement.     

Ectopic impulse generation and autoexcitation in single myelinated afferent fibers in patients with peripheral neuropathy and positive sensory symptoms

Microneurographic studies were performed using cutaneous nerves of 8 patients with documented peripheral neuropathy who expressed positive sensory symptoms. Intraneural recordings in single myelinated fibers revealed: (i) ectopic generation of bursts of spontaneous action potentials; (ii) ectopic generation of ongoing repetitive discharges transiently interrupted by natural stimulation of the receptive field; and (iii) repetitive discharges triggered by a preceding action potential. These results provide direct evidence of a peripheral pathophysiological basis for spontaneous and stimulus-induced paresthesias and dysesthesias in patients with peripheral neuropathy. © 1998 John Wiley & Sons, Inc. Muscle Nerve 21: 1661–1667, 1998     

Restless legs syndrome

Restless legs syndrome (RLS), first described in 1672 and given its name in 1945, is one of the most common sleep and movement disorders. Modern population-based studies demonstrate a prevalence between 5% and 15% in adult white populations. According to the diagnostic criteria, RLS is defined as an irresistable desire to move limbs, usually associated with paresthesias/dysesthesias and motor restlessness. The symptoms start or worsen at rest and improve with activity. Additionally, the symptoms worsen in the evenings and/or nights, which often results in disturbance of sleep with daytime tiredness. There is often a family history of RLS. Initially, the disease course is usually fluctuating and later may become continuous or chronic-progressive. The diagnosis is based on the patient history and is supported by a normal neurological examination. RLS is confirmed by the finding of periodic limb movements (PLM) in polysomnographic investigations and by a response to dopaminergic medication. A large number of studies have confirmed the effect of levodopa (L-dopa) in the treatment of RLS. A majority of the patients treated over a longer period of time with L-dopa, however, develop problems with an effect called augmentation, where the RLS symptoms begin appearing earlier during the day and involve new parts of the body with increasing severity. A large number of studies have now confirmed that dopamine agonists can also be effective in RLS therapy, and that this treatment seems to involve less risk for augmentation. This paper provides a general review of RLS with a focus on current treatment options.     

Perceived severity of restless legs syndrome across the female life cycle

BackgroundAs with migraine, female sex hormones may explain the high prevalence of restless legs syndrome (RLS) in women and therefore influence RLS severity across the female life cycle.Objective and methodsTo test this hypothesis, we performed a questionnaire-based transversal survey in female members of the French Association of patients with RLS. Five hundred thirty-six women fulfilled the RLS criteria and completed the International RLS Severity Scale (IRLSSS) and questionnaire about reproductive behaviour, RLS history and perception of RLS symptom severity during pregnancy, menses and menopause.ResultsPatients with at least one child showed a significantly higher mean IRLSSS score than women without children and 23% of the patients declared having perceived worsening of symptoms during pregnancy. Perceived RLS severity was increased during menses in 29% of non-menopaused patients and 69% of the patients reported worsening of symptoms following menopause. In these patients, a tendency towards higher IRLSSS scores was noted. Regression analysis revealed a correlation between higher IRLSSS scores and an early age at onset of RLS.ConclusionsFemale hormonal changes do not account for the variation in perceived severity in women with RLS during their hormonal milestones and their role in the pathophysiology of RLS is unlikely.