Mauro Manconi

Restless legs syndrome and pregnancy

Objective: To perform a large and detailed epidemiologic study on restless legs syndrome (RLS) during pregnancy and the puerperium. Methods: A structured clinical interview, assessing symptoms since the beginning of pregnancy, was performed to a population of 642 pregnant women at the time of delivery and at follow-up evaluation (1, 3, and 6 months after delivery). Main hematologic tests were also evaluated. A woman was considered affected if she met the International RLS Study Group criteria for RLS diagnosis. Results: Twenty-six percent of women were affected by RLS during their pregnancy. The disease was strongly related to the third trimester of pregnancy and tended to disappear reaching the time of delivery. Affected women presented lower values of hemoglobin and mean corpuscular volume compared with healthy subjects (both groups received the same supplemental iron and folate therapy). Conclusions: Pregnancy is associated with transient restless legs syndrome.

A quantitative statistical analysis of the submentalis muscle EMG amplitude during sleep in normal controls and patients with REM sleep behavior disorder

The aim of this study was to evaluate quantitatively the amplitude of the submentalis muscle EMG activity during sleep in controls and in patients with idiopathic REM sleep behavior disorder (RBD) or with RBD and multiple system atrophy (MSA). We recruited 21 patients with idiopathic RBD, 10 with MSA, 10 age‐matched and 24 young normal controls. The average amplitude of the rectified submentalis muscle EMG signal was used for the assessment of atonia and a Sleep Atonia Index was developed; moreover, also chin muscle activations were detected and their duration and interval analyzed. The Sleep Atonia Index was able to distinguish clearly REM from NREM sleep in normal controls with values very close to 1 in young normal subjects and only slightly (but significantly) lower in old controls. Idiopathic RBD patients showed a further significant decrease of this index; MSA patients showed the lowest values of REM Sleep Atonia Index, which were very well distinguishable from those of normal controls and of idiopathic RBD patients. The distribution of the duration of chin activations was monomodal in all groups, with idiopathic RBD patients showing the highest levels. This study is a really quantitative attempt to provide practical indices for the objective evaluation of EMG atonia during REM sleep and of EMG activations. Our proposed Sleep Atonia Index can have a practical application in the clinical evaluations of patients and represents an additional useful parameters to be used in conjunction with the other criteria for the diagnosis of this sleep motor disorder.

High prevalence of restless legs syndrome in multiple sclerosis

Despite the fact that multiple sclerosis (MS) patients often include leg restlessness as a sensory symptom, MS is not mentioned amongst symptomatic restless legs syndrome (RLS) forms. The aim of this study was to estimate RLS prevalence in a large population of MS patients, comparing clinical and MRI findings between patients with and without RLS. Each of the 156 MS patients (100 females, 56 males, mean age 40.7 ± 10.4) enrolled in a prospective study underwent a medical history interview, a neurological examination with the assessment of the Expanded Disability Status Scale (EDSS), and a structured questionnaire to verify the presence and features of RLS. Conventional brain–spinal MRIs of 99 subjects were also evaluated and compared between patients with and without RLS. Fifty‐one subjects (32.7%) (mean age 43.8 ± 12.8) met the criteria for RLS. In a few patients (8.5%), the RLS preceded clinical MS onset, whilst in the remaining cases the RLS was followed by or was simultaneous with clinical MS onset. Comparing the RLS group with the group without RLS, no significant differences were found in MS duration, gender, and referred sleep habits. The primary progressive MS course was more represented in the RLS group, which also showed a higher EDSS score. RLS is a very common finding in MS patients and should be considered amongst the symptomatic RLS forms. RLS is also associated with higher disability.

Dissociation of periodic leg movements from arousals in restless legs syndrome

The purpose of this study was to characterize the nature of the relation between periodic leg movements during sleep (PLMS) and cortical arousals to contribute to the debate on the clinical significance and treatment of PLMS.

Restless legs syndrome is a common finding in multiple sclerosis and correlates with cervical cord damage

In this prospective study, we estimated the prevalence of restless legs syndrome (RLS) in multiple sclerosis (MS) patients, and compared the extent of brain and cervical cord damage between patients with and without RLS using conventional and diffusion tensor magnetic resonance imaging (MRI). Eighty-two consecutive MS patients were evaluated. Each patient underwent a medical history interview, a neurological examination and brain/cervical cord MRI. Global and regional dual-echo lesion load (LL), number of cervical cord lesions, mean diffusivity (MD) and fractional anisotropy (FA) histograms metrics of the normal-appearing tissues of the brain and cervical cord were assessed. Thirty subjects had RLS; they showed a higher Expanded Disability Status Scale score than patients without. No difference between the two groups was found in whole brain, cerebellar and brainstem T2-LLs; MD and FA histograms derived metrics of the normal appearing brain tissues; basal ganglia MD; number of cervical cord lesions and cord MD histograms derived metrics. Cervical cord average FA was significantly reduced in MS patients with RLS compared to those without. RLS symptoms are very common in MS. This form of RLS should be considered as symptomatic. Higher disability and cervical cord damage represent a significant risk factor for RLS in MS patients. Multiple Sclerosis 2008; 14: 86—93. http://msj.sagepub.com

Improved computation of the atonia index in normal controls and patients with REM sleep behavior disorder

OBJECTIVE The aim of this study was to evaluate the effects of a simple method of noise reduction before the calculation of the REM sleep atonia index (AI) on a large number of recordings from different normal controls and patient groups. SUBJECTS AND METHODS Eighty-nine subjects were included: 25 young controls, 10 aged controls, 31 untreated patients with idiopathic REM sleep behavior disorder (iRBD), 8 treated patients with iRBD, 10 patients with multiple system atrophy (MSA) and 5 patients with obstructive sleep apnea syndrome (OSAS). The average amplitude of the rectified submentalis muscle EMG signal was then obtained for all 1-s mini epochs of REM sleep. The new correction method was implemented by subtracting from each mini epoch the minimum value found in a moving window including the 60 mini epochs surrounding it. RESULTS Two arbitrary thresholds were established at AI<0.8 and 0.8<AI<0.9; all young controls presented AI>0.9; this was not true for aged controls, 3 of whom presented 0.8<AI<0.9 but none had AI<0.8; on the contrary 74.4% of all iRBD showed AI<0.9, with 38.5% of the whole group having AI<0.8 and only 25.6% with AI>0.9. All MSA patients showed AI<0.8. CONCLUSIONS After the introduction of this new method for noise reduction, REM sleep AI index values lower than 0.8 were strongly indicative of altered (reduced) chin EMG atonia during REM sleep; values of AI between 0.8 and 0.9 indicated a less evident involvement of atonia, and values above 0.9 characterized the majority of normal recordings.

Measuring the error in sleep estimation in normal subjects and in patients with insomnia

The aims of this study were to measure the error in sleep estimation in normal controls and subjects with primary insomnia to establish the minimum amount of sleep needed for reliable subjective estimation and to depict the distribution of the error in sleep estimation in both groups. A two‐step retrospective (study 1) and prospective (study 2) validation study was carried out. Study 1 included 288 normal subjects [176 females and 112 males, mean age 58.5 years, standard deviation (SD) 7.23]. Study 2 included 159 patients (98 females and 61 males; mean age 49.1 years, SD 12.71) with primary insomnia. Participants underwent a full‐night polysomnographic study, followed by a morning assessment of subjective sleep parameters. A misperception index (MI) was computed using the following formula: MI = [objective total sleep time (oTST)−subjective total sleep time (sTST)]/oTST. The statistical properties of this index were analysed in detail in both groups. In controls, the Bland–Altman test demonstrated the reliability of this index for values of oTST >120 min. Healthy subjects estimated their sleep time correctly, while insomniacs largely underestimated their sleep time. Statistical analysis of the distribution of MI in insomnia patients disclosed the presence of two subgroups, one with moderate sleep misperception (132 patients) and the other with high sleep misperception (27 patients). The latter presented MI values ≥0.9, exhibiting statistical properties different from those with MI <0.9 and from normal subjects. The MI gives a reliable and immediate description of sleep misperception in healthy and insomnia subjects. Its application supports the existence of the high misperception of insomnia as a separate pathological entity.

Guidelines for the first-line treatment of restless legs syndrome/Willis–Ekbom disease, prevention and treatment of dopaminergic augmentation: a combined task force of the IRLSSG, EURLSSG, and the RLS-foundation

A Task Force was established by the International Restless Legs Syndrome Study Group (IRLSSG) in conjunction with the European Restless Legs Syndrome Study Group (EURLSSG) and the RLS Foundation (RLS-F) to develop evidence-based and consensus-based recommendations for the prevention and treatment of long-term pharmacologic treatment of dopaminergic-induced augmentation in restless legs syndrome/Willis-Ekbom disease (RLS/WED). The Task Force made the following prevention and treatment recommendations: As a means to prevent augmentation, medications such as α2δ ligands may be considered for initial RLS/WED treatment; these drugs are effective and have little risk of augmentation. Alternatively, if dopaminergic drugs are elected as initial treatment, then the daily dose should be as low as possible and not exceed that recommended for RLS/WED treatment. However, the physician should be aware that even low dose dopaminergics can cause augmentation. Patients with low iron stores should be given appropriate iron supplementation. Daily treatment by either medication should start only when symptoms have a significant impact on quality of life in terms of frequency and severity; intermittent treatment might be considered in intermediate cases. Treatment of existing augmentation should be initiated, where possible, with the elimination/correction of extrinsic exacerbating factors (iron levels, antidepressants, antihistamines, etc.). In cases of mild augmentation, dopamine agonist therapy can be continued by dividing or advancing the dose, or increasing the dose if there are breakthrough night-time symptoms. Alternatively, the patient can be switched to an α2δ ligand or rotigotine. For severe augmentation the patient can be switched either to an α2δ ligand or rotigotine, noting that rotigotine may also produce augmentation at higher doses with long-term use. In more severe cases of augmentation an opioid may be considered, bypassing α2δ ligands and rotigotine.

Neurophysiological study of corticomotor pathways in restless legs syndrome.

OBJECTIVE To test the variations in cerebral motor excitability in patients with primary restless legs syndrome (RLS) by using electrophysiological techniques. In RLS patients periodic legs movements (PLMs) in sleep and wake have been described and it is hypothesised that PLMs result from a sleep-related disinhibition of descending central motor inhibitory pathways. Moreover, in primary RLS, these modifications are still debated. METHODS In 15 patients with primary RLS, transcranial magnetic stimulation (TMS) was carried out using several paradigms, particularly paired pulse TMS with short interstimulus intervals (ISI) in abductor digiti minimi (ADM) and tibialis anterior (TA) muscles. RESULTS Short ISI paired TMS showed a significant decrease in inhibition and increase in facilitation in ADM muscles. This result was even more evident in TA muscles of patients as compared to the controls and these modifications were more evident in the limbs which were more affected by PLM. Moreover, intracortical (corticocortical) inhibition (ICI) and intracortical facilitation (ICF) unchanged their biphasic time course. CONCLUSIONS In our study the changes in short paired-pulse ICI and ICF revealed the presence of an altered excitability of central motor pathways, with good correlation with asymmetric distribution of symptoms.

Transient RLS during pregnancy is a risk factor for the chronic idiopathic form

Objective: Pregnancy is a risk factor for transient restless legs syndrome, which usually recovers during the postdelivery period. The goal of the present survey is to investigate whether restless legs syndrome during pregnancy represents a risk factor for later development of restless legs syndrome. Methods: A long-term follow-up study, planned as an extension of a previous survey on restless legs syndrome during pregnancy, was carried out. After a mean interval of 6.5 years, 207 parous women were contacted again to compare the incidence of restless legs syndrome among subjects who never experienced the symptoms with those who reported restless legs syndrome during the previously investigated pregnancy. Results: Seventy-four women who experienced restless legs syndrome during previous pregnancy, and 133 who did not, were included in the study. The incidence of restless legs syndrome was 56% person/year in women who experienced the transient pregnancy restless legs syndrome form, and 12.6% person/year in subjects who did not, with a significant 4-fold increased risk of developing chronic restless legs syndrome in women who presented restless legs in the previous pregnancy. Considering further new pregnancies during the follow-up period, the restless legs symptoms reappeared in 58% of the cases, while they emerged for the first time in only 3% of women who had never experienced restless legs syndrome. Conclusions: The transient pregnancy restless legs syndrome form is a significant risk factor for the development of a future chronic idiopathic restless legs syndrome form, and for a new transient symptomatology in a future pregnancy.