Prevalence and characteristics of right-to-left shunt in migraine with aura: a survey on 120 Italian patients

Many lines of research have suggested a relationship between migraine with aura (MA) and patent foramen ovale. Right-to-left shunt (RLS) of blood might explain both the occurrence of MA attacks, as well as the increased risk of ischaemic stroke in these patients. We evaluated the prevalence and the characteristics of RLS in a series of 120 MA patients, who were studied with contrast-enhanced Transcranial Doppler examination. We found RLS in 61 of them. A latent RLS was found in 28%, a permanent RLS in 72%, a shower-curtain pattern was detected in 52% of the studied patients.

     

Restless legs syndrome is not associated with migraine with aura: a clinical study

Based on recent data about the association between restless legs syndrome (RLS) and migraine, we performed an observational study on the occurrence of RLS in patients affected by “pure” migraine with aura (pMA). We recruited 63 patients (33 females and 30 males) affected by MA without other types of primary headache among all patients referred in five Italian headache centers in a 1-year period. The prevalence of RLS in pMA patients (9.5%) is similar to that observed in Italian headache-free subjects (8.3%). No significant differences were found between pMA patients with and without RLS about clinical features of MA attacks and systemic and psychiatric diseases were investigated. Moreover, no association appeared between RLS and familial cases of MA. Differently from migraine without aura, our data do not confirm the existence of an association between RLS and MA, not even when a genetic factor is involved.

     

High prevalence of Dopaminergic Premonitory Symptoms in migraine patients with Restless Legs Syndrome: a pathogenetic link?

In order to assess the prevalence of Dopaminergic Premonitory Symptoms (DPS) in migraine patients with Restless Legs Syndrome (RLS), we chose migraine patients from a large Italian clinical headache population previously investigated for an association between primary headaches and RLS. We evaluated a total sample of 164 patients with migraine, in particular 114 with migraine without aura (MO), 10 with migraine with aura (MA) and 40 with MO and MA in various combinations between them or with episodic tension-type headache (ETTH), defined as a “mixed group”. About 20% of all migraine patients referred at least one of the following DPS: yawning, nausea, somnolence or food craving, confirming data already indicated in the literature. Among migraine patients with RLS (25.6%), DPS were referred from about half of the patients (47.6%) compared to those without RLS (47.6% vs. 13.1%; p<0.001). Based on migraine subtype, patients with MO referred DPS (26.3%) more frequently compared to the MA group and “mixed group” (12.0%, p<0.05), particularly in the presence of RLS (63.0% vs. 20.0%, p<0.01). No statistical differences were found between clinical and demographic data of the subgroups or related to medical conditions investigated (anxiety, depression, sleep disorders, body mass index). It is interesting that the chances of having RLS in migraine patients were more than 5 times higher in the presence of DPS. These results could support a hypothetical dopaminergic imbalance in RLS and migraine, as the dopamine is involved in the pathogenesis of both disorders and it is responsible for the migraine DPS reported above.     

The extent of right-to-left shunt fails to correlate with severity of clinical picture in migraine with aura

Abstract Several investigations have documented an increased incidence of right-to-left shunt (RLS) in migraine with aura (MA) and have emphasised its role in the physiopathology of aura; so far, however, no data are available concerning a possible correlation between the extent of the RLS and the clinical picture of MA patients. To investigate the possible relationship between the extent of the RLS, revealed by the number of microbubbles (MB) detected during transcranial Doppler with IV injection of ultrasound contrast (TCDc), and the clinical characteristics of MA (age at first onset of migraine, mean annual frequency of attacks and mean duration of the aura phase), 30 consecutive patients with typical aura and migraine headache positive on TCDc evaluation for RLS were enrolled. Permanent RLS was found in 12 patients and latent RLS was found in 18 patients; of these, 6 had a high-grade RLS, 5 medium-grade RLS and 7 low-grade RLS. No correlation has been documented between the number of MBs and the clinical parameters of both patients with latent shunts and those with permanent ones, nor between the clinical parameters of the two groups of patients. These data show that RLS does not seem to affect the clinical manifestation of MA and that the extent of RLS fails to correlate with the severity of the clinical picture of the disorder.     

对比增强经颅多普勒对隐源性缺血性卒中和先兆性偏头痛患者与右向左分流不同分流量相关性的研究

目的 对隐源性缺血性卒中和先兆性偏头痛患者的右向左分流阳性率及分流量进行对比分析,研究二者之间右向左分流的特征及可能的发病机制.方法 连续入组48例隐源性缺血性卒中患者、42例先兆性偏头痛患者、33例健康志愿者做为对照组,使用对比增强经颅多普勒诊断右向左分流,并根据分流量进行分级,对3组的右向左分流阳性率和不同分级进行...     

Time course of arousal response during periodic leg movements in patients with periodic leg movements and restless legs syndrome.

OBJECTIVE: The temporal evolution of periodic leg movements (PLM) and the relationship of their arousing effect on sleep episode has not been extensively investigated. We studied the nocturnal evolution of PLM associated or not with microarousal (MA) and associated with slow wave activity (PLM with slow wave activity) in 23 patients with PLM and/or restless legs syndrome (RLS). METHODS: All subjects had PLM associated with MA or with slow wave activity as well as without MA and all slept for 4 sleep cycles. Spectral electroencephalogrpahic (EEG) analysis was done for the 4 sleep cycles to assess the nocturnal variation in slow wave activity (SWA). RESULTS: Sixty percent of PLM were associated with MA, 4% were associated with slow wave activity whereas 36% showed no EEG changes. There was a clear prevalence of PLM with MA in stages 1 and 2 while PLM without MA were prevalent in slow wave sleep. The night-time PLM index progressively declined from the first to the last sleep cycle (P<0.005), without differences between PLM types, or between PLM and RLS patients. The decline of PLM duplicated the temporal trend in SWA over consecutive sleep cycles. CONCLUSIONS: PLM showed a typical pattern of progressive decline throughout the night following the exponential decline in SWA. These over-time variations occurred independently of changes in the rate of PLM associated or not with MA or associated with slow wave activity, suggesting that variations in arousal threshold and sleep propensity did not affect the PLM arousing effect. The PLM-related arousal response might be affected by interaction of circadian and sleep stage influences with the addition of sleep oscillatory processes.     

Restless legs syndrome and primary headaches: a clinical study

Based on recent data about the association between restless legs syndrome (RLS) and migraine, we performed an observational study on the occurrence of RLS in patients affected by primary headaches. Two hundred headache patients (149 women and 51 men) and 120 (90 women and 30 men) sex-and age-matched control subjects were included. In the headache group, migraine without aura (MO) was the most represented headache type (n=114), followed by the “mixed” group (n=40) with MO, migraine with aura (MA) and frequent episodic tension-type headache (ETTH) in various combinations, and by ETTH alone (n=22). The remaining patients suffered from MA alone (n=10 MA), episodic cluster headache (ECH n=12) and primary stabbing headache (n=2). RLS frequency was significantly higher in headache patients than in control subjects (22.4% vs. 8.3, p=0.002) independently of sex, although with a female preponderance (84%) in both groups. More than 60% (n=27) of RLS patients were affected by MO and 30% (n=13) by a combination of two headache types (p≥0.001), with a very low frequency of RLS for the other types of headache. No RLS patient had ECH. No statistical differences were observed among clinical characteristics of different types of headache in groups with and without RLS. In both headache and control groups, higher scores for depression and anxiety were more frequent in subjects with RLS compared with those without RLS. Furthermore, headache patients with RLS reported sleep disturbances more frequently compared to those without RLS (50.0% vs. 32.7%; p<0.0001) and showed a normal or underweight body mass index. Our data seem to confirm the existence of an association between RLS and primary headaches, particularly with migraine, as already demonstrated. The absence of RLS in ECH patients is very interesting. Many pathogenetic considerations about links between RLS and primary headaches could be given, the most fitting involving dopamine and melatonin.     

Clinically significant but unsuspected restless legs syndrome in patients with sleep apnea.

In this prospective study, the prevalence of clinically significant restless legs syndrome (RLS) with symptoms at least 2 to 3 days per week was 8.3% in 60 sequentially polysomnographically studied patients with clinically significant sleep apnea (Apnea Index score > 5 or Respiratory Disturbance Index score > 10). Age-matched spouses were used as a control group and showed a comparable prevalence of RLS at 2.5% (not significant). Although RLS appears to be only slightly more common in sleep apnea patients than in controls, the importance of this study lies in the fact that clinically significant RLS occurred in 1 of every 12 patients with sleep apnea and, in every case, the RLS was unsuspected before polysomnography. We recommend that all patients undergoing polysomnography to rule out sleep apnea be screened for the symptoms of RLS. We have found the MEMO-NIH consensus conference questionnaire administered at the time of polysomnography to be useful in this regard.     

Restless legs syndrome is a common feature of adult celiac disease

Restless legs syndrome (RLS) is a common neurological condition, frequently idiopathic, sometimes associated with specific disorders such as iron deficiency. We investigated RLS prevalence in celiac disease (CD), an autoimmune disease characterized by several features such as malabsorption‐related iron deficiency anemia and peripheral neuropathy. We screened a population of 100 adult CD patients for CD features, iron metabolism, clinical and neurological conditions, and enrolled 100 age‐ and sex‐matched controls in the general population. RLS was ascertained in CD patients and controls by both the presence of the four essential International RLS Study Group diagnostic criteria and neurological examination. The International RLS Study Group rating scale was used to measure RLS severity. We found a 31% prevalence of RLS in the CD population that was significantly higher than the prevalence in the control population (4%; P < 0.001). The average severity of RLS in CD population was moderate (17 ± 6.5). In the CD population, no significant correlation was found between RLS and either gluten‐free diet or iron metabolism, despite hemoglobin levels were significantly lower in CD patients with RLS than without RLS (P = 0.003). We found no correlation between RLS and other possible causes of secondary RLS, including signs of peripheral neuropathy, pregnancy, end‐stage renal disease, and pharmacological treatments.Our study broadens the spectrum of neurological disorders associated with CD and indicates that RLS should be sought for in all patients with CD. © 2010 Movement Disorder Society     

中国偏头痛患者右向左分流阳性率及分流类型——一项全国多中心研究

背景 偏头痛与右向左分流（right-to-left shunt,RLS）的关系尚有争议。本研究旨在明确中国偏头痛 患者右向左分流的阳性率、分流类型以及分流量大小,分析偏头痛与右向左分流的关系。 方法 该研究为多中心-病例对照研究（北美临床研究注册号NCT0242569)。由中国9家分中心共同完 成,连续纳入2015年6月-2016年8月就诊于分中心且符合据第三版国际头痛疾病分类-β测试版（The International Classification of Headache Disorders 3rd Edition Beta Version,ICHD-3β）诊断偏头痛的患 者（18～65周岁）,为偏头痛组。偏头痛组共纳入931例（女性695例）,其中先兆偏头痛240例（女性174 例）,无先兆偏头痛691例（女性521例）。健康对照组共282例。 结果 先兆偏头痛组RLS阳性率和大量分流比例高于无先兆偏头痛组（63.7% vs 39.9%,P＜0.001; 32.1% vs 16.5%,P＜0.001）,两组中量和小量分流比例无差异（P =0.141;P =0.061）。无先兆偏头痛 组RLS阳性率和大量分流比例高于对照组（39.9% vs 29.4%,P＜0.001;16.5% vs 6.4%,P＜0.001）, 两组间中量和小量分流的比例无差异。 结论 偏头痛患者（包括有先兆和无先兆偏头痛患者）,右向左分流阳性率高于正常对照组,且以大 量右向左分流为主,中至小量右向左分流及分流的类型与对照组相比无差异。右向左分流,特别是大 量的右向左分流,可能与偏头痛有关。     

Restless legs syndrome: a clinical study of 55 patients

BACKGROUND: Restless legs syndrome (RLS) is a common sleep disorder. In 1995, clinical criteria for the diagnosis of RLS were defined. OBJECTIVE: To describe the clinical spectrum in a series of unselected RLS patients meeting the new diagnostic criteria. METHODS: We prospectively assessed by questionnaire and clinical assessment the characteristics of 55 consecutive RLS patients (35 women, 20 men; mean age = 62 +/- 16 years). RESULTS: In 27% of the patients, RLS started before the age of 20 years (early-onset RLS). Sensory disturbances were painful in 56% of patients and felt in legs (98%), arms (35%), and 'internally' (45%). Motor disturbances included 'dyskinesias while awake' (36%). Insomnia (58%) was commoner than hypersomnia (24%). In 67% of the patients, no etiology of RLS was found (idiopathic RLS). Early-onset RLS was more commonly familial (p = 0.01) and associated with 'growing pains' (p = 0.005) than late-onset RLS. Patients with RLS and hypersomnia were younger (p = 0.01) and less commonly had painful sensations (p = 0.04) than patients with RLS and insomnia. Patients with idiopathic RLS were younger (p = 0.004), and less commonly had insomnia (p = 0.01) than patients with symptomatic RLS. CONCLUSIONS: RLS is a clinically pleomorphic syndrome, reflecting the contribution of multiple genetic and acquired factors in the pathogenesis of RLS.     

Restless legs syndrome in hereditary spastic paraparesis

This study was designed to investigate the prevalence and determinants of the association of restless legs syndrome (RLS) and hereditary spastic paraparesis (HSP). Therefore, 132 patients with HSP were evaluated concerning the symptoms of RLS by a standardized questionnaire. RLS was supposed when patients met all of the established four essential criteria of RLS defined by the International RLS Study Group. In addition, we studied the relationship between RLS and age at HSP symptom onset and evaluated the severity of RLS symptoms. Out of 59 responses, RLS was found in 27 HSP patients (15 male, 12 female) so that RLS was more frequent in the total HSP group (20.5%; 27/132) than in previous population-based studies (about 11%). In all 27 patients, the diagnosis of RLS was established based on an additional personal interview. The probability to develop RLS did not increase with higher age. Age at onset of HSP symptoms in the HSP group with RLS (27.7 +/- 12.6 years) and the HSP group without RLS (37.0 +/- 16.9 years) differed significantly (p = 0.04). Most of the patients with RLS showed a moderate and severe grade on the RLS severity score. Only 8 patients had previously been diagnosed to have RLS and were on medication. The data of this screening for RLS provided evidence that patients with HSP are particularly susceptible to develop RLS. Consequently, special emphasis should be put on the diagnosis criteria of RLS in HSP patients.     

Prevalence of restless legs syndrome in blood donors

Iron deficiency anemia has been linked to restless legs syndrome (RLS) and regular blood donation may lead to iron deficiency. It has been reported that blood donations may be associated with RLS. A recent study from Sweden found that 25% of the women donors were affected by RLS. However, this type of study has not been replicated in the United States. We conducted a study in our blood donation unit between September and October 2008. To identify those with RLS, we used the RLS diagnostic index questionnaire by Benes et al. The proportion of blood donors with RLS was estimated and the number of blood donations and hemoglobin levels were compared according to RLS status. One hundred and fifty one patients were interviewed; 7 patients who donated only platelets were excluded, leaving 144 patients for analysis. There were 13 (9.0%, 95% confidence interval [CI]: 4.9–14.9%) patients with RLS. Of these, 7 (4.9%, 95% CI: 2.0–9.8%) had possible RLS and 6 (4.2%, 95% CI: 1.5–8.9%) had major or clinically relevant RLS. There was no dramatic association between RLS and number of blood donations or hemoglobin level (all P ≥ 0.21). In our sample of blood donors in the United States, the prevalence of major RLS was 4%. We could not demonstrate an association between RLS and the frequency of blood donation or hemoglobin level in our relatively small sample; a larger sample is needed to better identify any associations. © 2010 Movement Disorder Society     

Age and gender effects on heart rate activation associated with periodic leg movements in patients with restless legs syndrome.

OBJECTIVE: Periodic leg movements during sleep (PLMS) are often associated with electroencephalographic (EEG) changes, such as microarousals (MA), and with heart rate (HR) variations. The aim of the present study was to evaluate the effects of age and gender on HR changes associated with PLMS in restless legs syndrome (RLS) patients. METHODS: Forty-two RLS patients underwent one night of polysomnographic recordings. They were divided into 3 groups of 14 subjects (7 women and 7 men) according to age, i.e. young (25-40 years), middle-aged (41-55 years) and elderly (56-71 years) patients. The RR interval was calculated for 5 intervals before and 15 intervals after the onset of 50 PLMS in each patient. RESULTS: PLMS were associated with HR changes characterized by a tachycardia followed by a bradycardia. However, a reduction in the tachycardia and the bradycardia was observed with age. Moreover, women showed a higher amplitude in the bradycardia than men. No age or gender difference was found for MA index and duration. CONCLUSIONS: This study showed age and gender differences in the magnitude of the HR changes associated with PLMS. The knowledge of HR variations during sleep, including rapid HR changes associated with sleep events such as PLMS or MA, may be helpful in understanding the potential mechanisms involved in the increased cardiac risk observed in elderly.     

Restless legs syndrome in patients with chronic obstructive pulmonary disease

OBJECTIVE: To evaluate the prevalence of restless legs syndrome (RLS) in patients with chronic obstructive pulmonary disease (COPD) and the relationship between RLS and clinical/laboratory findings of COPD. METHODS: One hundred and thirty-four COPD patients without secondary causes of RLS were included. Thirty-nine (29.1%) patients were diagnosed with RLS and classified as Group 1. The control group consisted of 65 age-matched COPD patients without RLS. Group 1 was divided into subgroups according to the Johns Hopkins Severity (JHS) scale. Patients with a score of 0, 1, or 2 were classified as JHS 0-2 and those with a score of 3 as JHS 3. Group 1 and the control group and subgroups were compared for clinical and laboratory characteristics. RESULTS: We found that the duration of COPD was longer and that airway obstruction, hypercapnia, and hypoxia were more evident in patients with RLS than those without. Similar differences were also detected between JHS subgroups 3 (more severe) and 0-2. Polyneuropathy frequency was significantly higher in Group 1 compared to controls. However, Group 1 subgroups showed a similar frequency of polyneuropathy. In a multivariate analysis, hypercapnia made a significant independent contribution to both JHS 0-2 and JHS 3 patients when RLS severity was set as the dependent variable. Polyneuropathy and the duration of COPD were significant independent variables for patients in the JHS 3 subgroup. Polyneuropathy was the strongest predictor for the JHS 3 patients. CONCLUSIONS: We conclude that RLS is frequent in COPD, particularly in patients with severe hypoxemia/hypercapnia and in late stages of the disease.     

Restless legs syndrome in 218 patients: associated disorders

Background: Restless legs syndrome (RLS) is a disorder characterized by disagreeable sensations in the legs that occur at rest and are relieved by movement. These symptoms, which are worse at night, may result in sleep onset or sleep maintenance insomnia. Most patients are found on polysomnography (PSG) to have periodic limb movements in sleep (PLMS). The disorder, idiopathic in most cases, may be sometimes associated with specific disorders.Methods: Using the Province of Manitoba Health database, we compared the diagnoses made in the 5 years prior to sleep laboratory evaluation of 218 patients (103 men and 115 women) with RLS and 872 matched control subjects from the general population.Results: We found that 43.7% of male RLS patients vs. 10.4% of male controls and 46.1% of female RLS patients vs. 22.8% of female controls had been diagnosed as having psychological/psychiatric (most often depression) disorders (P<0.05). Extrapyramidal disease or movement disorders were previously diagnosed in 17.5% of male RLS patients vs. 0.2% of male controls and in 23.5% of female patients vs. 0.2% of female controls (P<0.05). Many patients had been previously diagnosed with disorders of the musculoskeletal system: 35.9% of male patients vs. 22.8% of male controls and 49.6% of female RLS patients vs. 23.3% of female controls had been diagnosed as having diseases of joints (male; P=ns, female; P<0.05). Disorders of the back were also more frequently diagnosed in RLS patients: 21.4% of male patients vs. 13.1% of male controls and 38.3% of female patients vs. 15.0% of female controls (male; P=ns, female; P<0.05).Conclusions: We conclude that RLS patients are much more likely to have previously been diagnosed with extrapyramidal disorders, musculoskeletal disorders, depression, and painful conditions such as joint and back disorders.     

Detektion kardialer und extrakardialer Rechts-links-Shunts bei jüngeren Schlaganfallpatienten

BACKGROUND: The aim of this study was to determine the frequency of extracardial and particularly pulmonal right-to-left-shunts (RLS) in patients with acute cerebral ischemia of unknown origin. PATIENTS AND METHODS: We investigated 52 patients under 60 years of age with cerebral ischemic stroke of unknown origin using transesophageal echocardiography (TEE) with special attention to the late phase of ultrasound contrast medium in the left atrium. Additionally we performed contrast transcranial doppler sonography (TCD). RESULTS: In the TEE, 25 patients (48%) showed cardial RLS. In seven patients with normal TEE (13.5%) we found evidence of RLS with contrast TCD (spontaneous RLS n=4, RLS after valsalva n=3). In none of these seven patients did we find late-phase contrast in the left atrium. CONCLUSION: The constellation of RLS detection in contrast TCD but not in TEE was frequently found. Particularly in spontaneous RLS, this constellation raises the suspicion of a pulmonary shunt. However our extended TEE protocol did not give additional evidence for a pulmonary location of the shunt.     

Lesion patterns in patients with cryptogenic stroke with and without right-to-left-shunt

Background and purpose:  Despite numerous studies, the role of patent foramen ovale (PFO) as a risk factor for stroke due to paradoxical embolism is still controversial. On the assumption that specific lesion patterns, in particular multiple acute ischaemic lesions on diffusion-weighted magnetic resonance imaging, indicate a cardioembolic origin, we compared the MRI findings in stroke patients with right-to-left shunt (RLS) and those without.
Methods:  The records of 486 patients with diagnosis of cerebral ischaemia were reviewed. For detection of RLS, contrast-enhanced transcranial Doppler (c-TCD) was carried out in all patients. An MRI scan of the brain was performed in all patients. Affected vascular territories were divided into anterior cerebral artery, middle cerebral artery, vertebrobasilar artery system including posterior cerebral artery, brain stem and cerebellar stroke, and strokes occurring in more than one territory.
Results:  We did not find a specific difference in neuroradiological lesion patterns in patients with RLS compared with patients without RLS. In particular, 23 of 165 patients (13.9%) with RLS showed multiple ischaemic lesions on MRI in comparison with 45 of 321 patients (14.0%) without RLS ( P  = 0.98). These findings also applied for the subgroup of cryptogenic strokes with and without RLS.
Conclusion:  We found no association between an ischaemic lesion pattern that is considered as being typical for stroke due to cardiac embolism and the existence of PFO. Therefore, our findings do not provide any support for the common theory of paradoxical embolism as a major cause of stroke in PFO carriers.     

Increased Frequency of Restless Legs Syndrome in Myasthenia Gravis

Background/Aims: The objective of this study was to assess the prevalence of restless legs syndrome (RLS) in patients with myasthenia gravis (MG). Methods: We interviewed 73 MG patients and 65 healthy controls by using a structured diagnostic questionnaire based on the International Restless Legs Syndrome Study Group diagnostic criteria. We also collected data about the course of MG therapy, the presence of other comorbidities, sleep complaints, and demographic characteristics. All of the MG patients underwent neurological assessment. Results: RLS was present in 43.2% of the MG patients and in 20% of the controls (p = 0.0029). We failed to identify a relationship between the prevalence of RLS and the duration and type of MG therapy, other comorbidities, age or sex of the patients. Patients with MG more frequently reported daytime sleepiness. For 9.4% of the RLS-positive MG patients, RLS symptoms represented the most disturbing health problem; for 46.9% of them, RLS was as problematic as other diseases. Conclusions: RLS is common in MG patients. MG patients consider RLS symptoms as a troublesome health problem.     

Restless legs syndrome in chronic inflammatory demyelinating polyneuropathy

The prevalence of restless legs syndrome (RLS) is unknown in chronic inflammatory demyelinating polyneuropathy (CIDP). We prospectively studied 28 patients with CIDP. Prevalence of RLS in CIDP was ascertained by face‐to‐face interview using validated criteria and compared with that in 28 age‐ and gender‐matched controls. Eleven (39.3%) CIDP patients were diagnosed with RLS, compared with 2 (7.1%) controls (P < 0.01). A significant correlation was ascertained between presence of RLS and lower limb weakness, functional disability, and summated compound muscle action potential (CMAP). The prevalence of RLS in CIDP was significantly higher than in controls in our study population, approaching 40%. Screening for RLS in CIDP patients may be appropriate, particularly in those with weakness, disability, and motor axonal loss in the lower limbs. Our findings may otherwise suggest the existence of peripheral components to the pathophysiology of RLS in patients with CIDP. Muscle Nerve, 2010