Autosomal dominant cerebellar ataxia type I: oculomotor abnormalities in families with SCA1, SCA2, and SCA3

Forty-six patients suffering from autosomal dominant cerebellar ataxia type I (ADCA I) underwent to a genotype-phenotype correlation analysis by molecular genetic assignment to the spinocerebellar ataxia type 1, 2, or 3 (SCA1, SCA2, SCA3) genetic locus and electro-oculography. Oculomotor deficits that are attributed to dysfunction of cerebellar structures occurred in all three mutations without major differences between the groups. Gaze-evoked nystagmus, however, was not found to be associated with SCA2. Square wave jerks were exclusively observed in SCA3. The gain in vestibulo-ocular reflex was significantly impaired in SCA3 and SCA1. In SCA3 the severity of vestibular impairment increased with CAG repeat length. Severe saccade slowing was a highly characteristic feature of SCA2. In SCA3 saccade velocity was normal to mildly reduced while SCA1 fell into an intermediate range. The present data show that each mutation is associated with a distinct syndrome of oculomotor deficits. Reduced saccade velocity and the absence of both square-wave jerks and gaze-evoked nystagmus allow one SCA2 to be distinguished from SCA3 patients in almost all cases. The eye movement disorder of SCA1 patients, however, overlaps with both SCA2 and SCA3. Received: 9 September 1998 Received in revised form: 18 February 1999 Accepted: 23 February 1999     

Restless legs syndrome in an Indian urban population

BACKGROUND: The prevalence of restless legs syndrome (RLS) in India is unknown. OBJECTIVES: The primary objective was to assess the occurrence of RLS in residents of Bangalore. The secondary objective was to correlate demographic and socioeconomic factors with RLS occurrence and severity. METHODS: This was a cross-sectional, questionnaire-based survey conducted during August 2005 among adult residents of Bangalore, who participated in a face-to-face interview. Diagnosis of RLS was based on fulfillment of all National Institutes of Health/International Restless Legs Syndrome Study Group (NIH/IRLSSG) essential criteria. Severity of RLS was assessed using the IRLSSG scale. RESULTS: RLS occurred in 27 (2.1%) of 1266 respondents. Predominant symptoms included "pulling," "tingling" and "pain". RLS was associated with delayed sleep onset and RLS severity correlated with the duration of delay in sleep onset. RLS was associated with per-capita income less than the equivalent of US$1/day, education less than high school level, chronic daily alcohol consumption and chronic blood loss. CONCLUSION: This is the first Indian population study on RLS which reveals prevalence of the disorder in a South Indian urban population at 2.1%. Larger studies are warranted to better characterize RLS in India.     

Restless legs syndrome in Friedreich ataxia: A polysomnographic study

Friedreich ataxia (FA) is the most common type of hereditary ataxia. Frataxin deficiency due to a GAA expansion in the first intron of chromosome 9 results in intramitochondrial iron accumulation. On the basis of the patients' complaints about sleep disturbance and pathophysiological considerations, we systematically assessed sleep history and polysomnography in FA. We included 16 consecutive FA patients (11 men, 5 women; mean age, 35.4 ± 11.1 years) with a mean disease duration of 16.5 ± 7.0 years. All patients underwent a standardized protocol including a detailed sleep history and polysomnographic recordings. Eight out of 16 patients were diagnosed with restless legs syndrome (RLS). In seven patients, RLS onset was after the onset of FA. Interestingly, FA patients with RLS had significantly lower serum ferritin levels than FA patients without RLS (76.3 ± 56.0 μg/L vs. 176.3 ± 100.7 μg/L; P = 0.043 after correction for sex and age). Moreover, periodic leg movements in wakefulness (PLMW) indices were significantly higher in FA patients with RLS than FA patients without RLS (FA with RLS, 118.1 ± 50.7; FA without RLS, 65.6 ± 44.2; P = 0.028). There was an inverse correlation between serum ferritin levels and PLMW indices obtained in all FA patients (rho ?0.538, P = 0.039). RLS is common in FA. Its frequency in this primarily spinal ataxia appears consistent with the concept of dysfunctional spinal sensorimotor integration in the pathophysiology of RLS. The finding that RLS is more frequent in the context of lower serum ferritin levels in FA is interesting, but requires further investigation in larger patient samples. © 2009 Movement Disorder Society.     

Restless legs syndrome and pregnancy: A review

Restless legs syndrome (RLS) is a common sensorimotor neurological disorder that is diagnosed according to the revised criteria of the International RLS Study Group (IRLSSG). The pathophysiology of RLS is still unknown and its prevalence is influenced by ethnicity, age, and gender. RLS is divided into two types by etiology: primary or idiopathic and secondary. Primary RLS is strongly influenced by a genetic component while secondary RLS is caused by other associated conditions such as end-stage renal disease or peripheral neuropathy. Another common condition associated with RLS is pregnancy. The prevalence of RLS during pregnancy is two to three times higher than in the normal population and is influenced by the trimester and the number of parity. The main mechanisms that may contribute to the pathophysiology of RLS during pregnancy are hormonal changes and iron and folate status. Standard medications for treating RLS during pregnancy are not established. Most medications have been used according to the evidence from non-pregnant patients. Therefore, consideration of the medical treatment for treating RLS during pregnancy should be balanced between the benefit of relieving the symptoms and maternal and fetal risk. In general, the prognosis of RLS during pregnancy is good and symptoms are usually relieved after delivery.     

Restless legs syndrome is highly prevalent in patients with post-polio syndrome

ObjectiveFew studies have quantified the prevalence of restless legs syndrome (RLS) in patients with post-polio syndrome (PPS). Our objective was to assess the prevalence and severity of RLS in patients with PPS and to examine the demographic characteristics of this population.MethodThis was a cross-sectional study conducted from April 2010 to May 2012 at the outpatient Neuromuscular Disorders clinic of Universidade Federal de São Paulo, São Paulo, Brazil. We evaluated 119 patients with PPS, consecutively recruited, and investigated for RLS based on the diagnostic criteria established by the International Restless Legs Syndrome Study Group (IRLSSG). Patients were evaluated with the Brazilian version of the IRLSSG severity scale.ResultsThe prevalence of RLS was 36% (n = 43; 32 women and 11 men). The ages at onset of RLS (median = 41 years) and PPS (median = 41 years) were concurrent, and the correlation between onset of symptoms of RLS and onset of symptoms of PPS was positive and very strong (Spearman r = 0.93, p = 0.01). The median RLS severity was 23 (range, 20–28). Low educational achievement and depression were predictive of RLS development.ConclusionIn the largest population of patients with PPS studied to date, our results indicate a high prevalence of RLS, marked disease severity, and concomitant onset of both conditions in many patients with PPS. Further studies are needed to elucidate a possible pathophysiologic mechanism linking these two conditions. We suggest that all post-polio patients with sensory and motor complaints in the legs be investigated for RLS.     

Restless legs syndrome and akathisia as manifestations of acute pontine infarction

Although restless legs syndrome (RLS) and akathisia have similar clinical manifestations and seem to share a common pathophysiology, they are regarded as distinct clinical syndromes. We present three patients with acute pontine infarction and RLS or akathisia as clinical manifestations. They presented with abrupt onset of restlessness of various body parts, as well as other neurological signs including dysarthria or weakness of the legs. Brain MRI of all three patients showed acute pontine infarction. The clinical syndrome in two of the patients was compatible with RLS and one with akathisia. Their symptoms improved after a brief period. Our finding of secondary RLS and akathisia as manifestations of acute pontine infarction provides information that assists in understanding the common anatomical and pathophysiological basis of RLS and akathisia.     

不宁腿综合征23例临床分析

目的 探讨不宁腿综合征(RLS)的临床表现及可能的发病机制,观察多巴丝肼对RLS的治疗效果.方法 对符合原发性RLS诊断标准的23例患者进行回顾性分析.结果 23例患者均为中老年人,平均年龄56岁,平均发病年龄52岁.常以失眠和白日嗜睡为主诉,根据国际不宁腿综合征研究组(IRLSSG)的诊断标准,平均得分为25分,其中16例(69%)的患者为重度(21～30分).多导睡眠图(polysomnography,PSG)检查发现18例(78%)合并有周期性肢动,其中11例(61%)的患者周期性肢动指数为中度(25～49次);所有患者微觉醒指数均增高,其中16例(67%)的患者为中度.经多巴丝肼125 mg每晚睡前服用,治疗4周后,多数患者主观症状明显改善,IRLSSG评分明显减少(平均得分13分),其中5例恢复正常;合并周期性肢动的患者中,5例周期性肢动指数恢复正常,其余患者均为轻度;微觉醒指数明显减少,其中11例降为正常;19例患者睡眠潜伏期转为正常.6例(26%)患者出现一过性头痛、恶心、嗜睡.结论 对下肢不适感觉、活动后减轻、合并睡眠中腿动的患者,应尽早检查;多巴丝肼对治疗RLS有一定疗效.     

随访十年的脊髓小脑性共济失调3型一家系研究及伦理学分析

目的 探讨随访十年的脊髓小脑性共济失调3型(SCA3)一家系的临床特征、影像学特点和基因型及其所带来的医学伦理学问题。方法 描述一家系7例患者的临床表现,对部分患者行头颅核磁共振及基因检测,结合文献复习并分析该家系中患者的临床表现、遗传特征,且进行相关的伦理学分析。结果 一家系4代21名成员中共有7例发病,以步态不稳和言语不清为突出表现,头颅MRI示小脑萎缩,其中4例患者基因检测SCA3相关基因的CAG重复数分别为76、77、76、78次,1例症状前患者为77次。结论 SCA3为一组神经系统遗传性疾病,临床特征以小脑性共济失调和构音障碍为突出表现,具有高度异质性,CAG 重复序列数目的检测对于基因诊断和症状前诊断是一种十分有效的方法。临床要严格按照医学伦理规范进行严谨的遗传检测。长期随访促进家族成员进行基因筛查,有助于发现症状前患者及促进产前诊断和优生优育。     

Frequency analysis and clinical characterization of different types of spinocerebellar ataxia in Serbian patients.

The relative frequencies of different spinocerebellar ataxias (SCAs) vary widely among different ethnic groups, presumably due to a founder effect. We investigated the relative prevalence of SCA1-3, 6-8, 12, 17; dentate-rubro-pallidoluysian atrophy; and Friedreich's ataxia (FRDA) in Serbian patients with adult-onset (>20 years of age) hereditary and sporadic SCAs, and compared clinical features of patients with genetically confirmed SCAs. A total of 108 patients from 54 families (38 apparently dominant [ADCA] and 16 apparently recessive) with adult-onset hereditary ataxia and 75 apparently sporadic patients were assessed. Of 38 families with ADCA, 13 (34%) were positive for an expansion in an SCA1 and 5 families (13%) for an expansion in an SCA2 allele. In 20 families (53%), no expansions have been identified in any of the analyzed genes. Gaze palsy, spasticity, and hyperreflexia were significantly more common in SCA1, whereas slow saccades, hypotonia, hyporeflexia, and dystonia prevailed in SCA2 patients. Among the 16 families with an apparently recessive mode of ataxia inheritance, 4 (25%) were identified as having the FRDA mutation. Ataxia-causing mutations were identified in 8 (10.6%) of patients with apparently sporadic adult-onset ataxia.     

Restless legs syndrome, insomnia, and quality of life after renal transplantation

OBJECTIVE: Restless legs syndrome (RLS) is associated with insomnia and impaired quality of life (QoL) in patients on maintenance dialysis; however, no information has been published on the association of RLS and QoL in kidney-transplanted patients. In a cross-sectional study, we analyzed the complex relationship between RLS, insomnia, and health-related QoL in kidney-transplanted patients. METHODS: In a cross-sectional survey at a single transplant center, 1067 patients were invited to participate. Complete data set was available from 785 kidney-transplanted patients. The RLS Questionnaire and the Athens Insomnia Scale were used to assess the prevalence of RLS and insomnia, respectively. QoL was measured using the Kidney Disease QoL-SF Questionnaire. RESULTS: Patients with RLS were three times more likely to have insomnia than patients without RLS (29% vs. 9%, P=.001), and the presence of RLS was a significant and independent predictor of insomnia in multivariate analysis. The presence of RLS was independently associated with impaired health-related QoL along several QoL domains after statistical adjustment for clinical and sociodemographic covariables. Importantly, this association remained significant even after adjusting for insomnia for some QoL domains. CONCLUSION: RLS is associated with poor sleep, increased odds for insomnia, and impaired QoL in kidney-transplanted patients. Our results suggest that both sleep-related and sleep-independent factors may contribute to the association of RLS and QoL.     

Spinocerebellar ataxia type 1, 2, and 3 and restless legs syndrome: striatal dopamine D2 receptor status investigated by [11C]raclopride positron emission tomography.

In spinocerebellar ataxias (SCAs), up to 30% of patients complain of restless legs syndrome (RLS). In primary RLS, a putative role of the dopaminergic system has been postulated. To assess dopaminergic function in SCA1, 2, and 3, dopamine D(2) receptor binding potential (BP) was assessed by [(11)C]raclopride positron emission tomography in 10 SCA patients, 4 of whom suffered from RLS as demonstrated by polysomnography. BP was compared to 9 age-matched control subjects. In 2 SCA patients, striatal BP was clearly reduced (<2 SD below the mean of controls). However, there were no significant group differences between SCA and controls, largely owing to a significantly higher variance of striatal BP in SCA. BP was negatively correlated with disease duration. The fit suggests an increased BP in early stages, followed by a moderate decline in all quantified regions (caudate, dorsal putamen, ventral striatum) presumably reflecting a progressive loss of D(2) receptors. RLS in SCA was not accompanied by a significant reduction of D(2) receptor availability in the striatum. This missing correlation may point to an extrastriatal origin of RLS.     

不宁腿综合征与认知障碍的前瞻性研究:基于社区的5年纵向队列研究

目的探讨不宁腿综合征(RLS/WED)与认知功能减退间的关系。方法这是一项基于上海黄浦区五里桥社区≥50岁人群的前瞻性研究。首先于2009年,使用中国版简易精神状态检查量表(MMSE-C)对该社区中222例RLS/WED患者(基于2003版诊断标准制定的量表筛查)和1669例无RLS/WED患者进行认知功能评定,通过问卷调查和病案回顾的方法收集混杂因素信息,建立基线标准,5年后(2014年)随访该人群的认知功能(MMSE-C)。通过Logistic regression方法分析RLS/WED人群与认知功能减退的相关性。结果仅调整年龄和性别后,RLS/WED对认知能力减退有保护作用(OR=0.68, 95%CI:0.46~0.99,P=0.04)。然而,继续调整其他混杂因素(包括性别、年龄、职业、教育状况、糖尿病、高血压、鼾症、失眠、吸烟和饮酒、体重指数、载脂蛋白Eε4、抑郁、头部创伤史、全身麻醉史、冠状动脉疾病史、脑梗死、脑出血史)后,RLS/WED和认知能力减退无显著相关性(OR=0.64, 95%CI:0.40~1.04,P=0.07)。结论基于社区随访5年的前瞻性研究未发现RLS与认知功能减退有相关性。     

继发性不宁腿综合征

本文回顾继发性不宁腿综合征的相关研究结果,介绍其常见病因。经研究显示,有多种因素可能与继发性不宁腿综合征的发生发展和严重程度相关,如肾衰竭、脊髓和周围神经病变、妊娠所致铁和叶酸缺乏及相应性激素变化;帕金森病多巴胺能系统功能紊乱;某些药物（抗抑郁药、抗精神病药、组胺受体阻断药）;吸烟、饮酒;咖啡因;偏头痛等。临床应详细询问病史,去除病因,提高患者生活质量。     

Restless legs syndrome,a predictor of subcortical stroke: a prospective study in 346 stroke patients

ObjectiveThe objective of this study was to assess the prevalence of restless legs syndrome (RLS) among patients with stroke and to examine the anatomical correlation between location of stroke and RLS symptoms.MethodsWe administered a pre-structured sleep questionnaire to consecutive stroke patients seen in our neurology services department over a 3-year period. Unconscious (Glasgow Coma Scale score <15) or aphasic, renally impaired, or neuropathic patients were excluded. Diagnosis of RLS was established according to the criteria of the International Restless Legs Syndrome Study Group (IRLSSG), and polysomnography was conducted.ResultsOf 346 stroke patients, 35 (10.11%) fulfilled IRLSSG diagnostic criteria for RLS, which had existed for an average (±standard deviation) of 60 ± 40 months before stroke. The mean age of onset was 52.94 (±10.32) years. Twenty-four patients (68%) had RLS symptoms contralateral to the hemisphere involved in the stroke (eight with unilateral and 16 with grossly asymmetrical RLS). Twenty-nine of 35 patients (82.86%) had imaging evidence of subcortical (16 with hemorrhagic and 13 with ischemic) stroke. Patients with pre-stroke RLS differed from those without it only by subcortical location of the stroke (82.9% vs 31.5% respectively, p < 0.001). The most significant differentiating factor between patients with subcortical stroke and those with cortical stroke was pre-stroke RLS (22.83% vs 2.74%, p < 0.001), the others being history of hypertension and hemorrhagic stroke type.ConclusionRLS, especially unilateral or asymmetrical, might frequently pre-exist in patients presenting with subcortical stroke. The common laterality may suggest an important predictive value for RLS, and may form an important point for future research.     

Clinical and molecular studies of 73 Italian families with autosomal dominant cerebellar ataxia type I: SCA1 and SCA2 are the most common genotypes

We clinically and genetically evaluated 73 Italian families with autosomal dominant cerebellar ataxia (ADCA) type I. Spinocerebellar ataxia (SCA) type 1 was the most common genotype (SCA1), accounting for 41% of cases (30 families), SCA2 was slightly less frequent (29%, 21 families), and the remaining families were negative for the SCA1, SCA2, and SCA3 mutations. Among the positively genotyped families, SCA1 was found most frequently in families from northern Italy (50%), while SCA2 was the most common mutation in families from the southern part of the country (56%). Slow saccades and decreased deep tendon reflexes were observed significantly more frequently in SCA2 patients, while increased deep tendon reflexes and nystagmus were more common in SCA1. In SCA1 and SCA2 families there was a significant inverse correlation between expansion size and age at onset. Analysis of triplet repeat numbers in parent-offspring pairs showed greater meiotic instability, which was associated with an earlier onset of the disease in SCA2 families than in SCA1 families. Received: 23 April 1998 Received in revised form: 14 September 1998 Accepted: 13 October 1998     

Restless legs syndrome and periodic limb movement disorder in the elderly

Restless legs syndrome (RLS) is a sensorimotor neurological disorder characterized by an urge to move the extremities, mostly the legs, caused or accompanied by unpleasant sensations in the affected limbs. Symptoms appear or increase in the evening or during the night and at rest. Sleep disturbances are the most frequent reason why patients seek medical aid. The diagnosis of periodic limb movement disorder (PLMD) requires polysomnographic confirmation and relies on the exclusion of other causes of sleep disturbances. The diagnosis of RLS is a clinical one and usually based on the patient's history. Diagnosis criteria should be applied in a modified form in the cognitively impaired elderly. The newly revised criteria emphasize behavioral indicators and supportive features in diagnosing RLS in this special population. Prevalence of both disorders increases strongly with age. Epidemiological studies revealed a 9% to 20% prevalence of RLS and an estimated 4% to 11% prevalence of PLMD in the elderly. Recent studies indicate RLS occurring approximately twice as often in older women than in older men. Treatment with dopaminergic drugs, opioids, anticonvulsants or hypnotics are usually well tolerated in the elderly. However, interaction with other medications and the possibility of severe sedation due to slower metabolism in the elderly should be considered.     

不安腿综合征的诊治

目的 探讨不安腿综合征(RLS)的临床特征,为早期诊断和治疗提供参考.方法 结合相关文献,对16例确诊的不安腿综合征患者的临床表现、治疗、转归进行回顾性分析.结果 RLS是一种以双下肢感觉异常不适为主要症状的病因未明的疾病,可能与贫血、铁缺乏、糖尿病史、肾功能不全等有关.多巴胺受体激动剂为治疗该病的首选药,阿片类、抗惊厥药物、苯二氮类药物及铁剂治疗对部分患者有效.结论 RLS预后较好,及时的诊断和治疗可明显改善患者的生活质量.     

Frequency of spinocerebellar ataxia mutations in the Kinki district of Japan

OBJECTIVES: To determine the frequencies of spinocerebellar ataxias (SCAs) in the Kinki district, the western part of the main island of Japan. MATERIAL AND METHODS: One hundred and forty-three families with dominantly inherited ataxia and 220 patients with apparently sporadic cerebellar ataxia were examined for the SCA1, SCA2, SCA3/Machado-Joseph disease (MJD), SCA6, SCA7, SCA8, SCA12 and dentatorubral-pallidoluysian atrophy (DRPLA) mutations. RESULTS: Among the dominant families, SCA1 accounted for 3%, SCA2 for 4%, SCA3/MJD for 24%, SCA6 for 31% and DRPLA for 12%. Neither SCA7 nor SCA12 mutations were detected. Among the apparently sporadic patients, 15% were found to have expanded triplet repeats. Of these, the SCA6 mutation was most frequently detected. CONCLUSION: SCA6 is the most common SCA in the Kinki district of Japan. Comparison of our results with those from other regions of Japan and different countries shows geographic and ethnic variation in the frequency of SCAs.