Variable expressivity in familial restless legs syndrome.

A 62-year-old man with a 20-year history of excessive daytime somnolence and kicking during sleep was an obligate carrier of the restless legs syndrome gene because his paternal grandfather, father, and all three of his children had symptoms of restless legs syndrome. The patient himself, however, denied motor restlessness after a careful and exhaustive medical history and he was originally believed to have periodic movements in sleep without restless legs. Close clinical observation did reveal nighttime motor restlessness, although the patient continued to deny its importance. Polysomnography showed frequent periodic movements in sleep. We conclude that there can be variable expressivity of the clinical features in familial restless legs syndrome and that there are probably some relatively nonrestless patients with prominent periodic movements in sleep who are carriers of the restless legs syndrome gene. Some sleep-disordered patients who are believed to have only periodic movements in sleep may have a forme fruste of autosomal dominant restless legs syndrome. If one does not examine these patients carefully at night and take an adequate family history, one may miss the diagnosis of restless legs syndrome.

A questionnaire study of 138 patients with restless legs syndrome: the 'Night-Walkers' survey.

After verifying the diagnosis of restless legs syndrome (RLS) in 105 patients who are part of a nationwide support group, we undertook a telephone survey of their symptomatology. We then compared the answers with those of 33 of our own RLS patients who had undergone a neurologic examination and had a periodic limb movement in sleep (PLMS) index of > 5 (number per hours of sleep). Although RLS has generally been considered to be a condition of middle to older age, the results for the support group, and for our patients, are similar in that more than a third of the patients in each group experienced their first symptoms before the age of 10. Initial lack of diagnosis or misdiagnosis by a physician were common and the symptoms were commonly thought to be psychogenic whatever the age of onset. In some cases, young age-onset RLS was severe from the start. For younger age-onset patients whose symptoms were severe enough to seek immediate medical attention, confounding or misdiagnosis included "growing pains" and attention deficit hyperactivity disorder. However, medical attention was generally not sought until the fourth decade. Most respondents stated that this was because their symptoms were mild at onset and then progressed. In the older age-onset patients, misdiagnoses also included skin irritation, arthritis, and malingering. A total remission of symptoms of a month or more was present in at least 15% of the individuals in all groups surveyed. More than 50% of the respondents know of one or more first-degree relatives affected by RLS. Five of our 33 patients had RLS initially triggered either by diabetic peripheral neuropathy or lumbosacral radiculopathy.

Moderate to severe periodic limb movement disorder in childhood and adolescence.

The purpose of this study is to review clinical features of children with moderate to severe Periodic Limb Movement Disorder (PLMD). Because of our interest in both Restless Legs Syndrome (RLS) and Attention-Deficit Hyperactivity Disorder (ADHD), many of our patients had one or both of these conditions. We did a retrospective review of 129 children and adolescents who were found to have Periodic Limb Movements in Sleep (PLMS) > 5/hour of sleep. Sixty five had PLMS of 5-10/hour of sleep, 48 had PLMS of 10-25/hour of sleep and 16 had PLMS > 25/hour of sleep. One hundred and seventeen of the original 129 had ADHD. Stimulant medication did not seem to play a role in the production of PLMS. In only 25 of the 129 cases did parents note the presence of PLMS before being specifically asked to look, and even after specific instructions to look, PLMS were not noted by the parents in 39 patients. The sub-group of 16 children and adolescents--6 female, 10 male (average age 11.1 years--range 6-17 years) with moderate to severe PLMS > 25/hour of sleep are described in more detail. Fifteen of the 16 patients had ADHD. Four of the 16 had RLS and 10 of 13 patients for whom a family history was available had a parent with RLS. Two of the 16 patients had their PLMS initially misdiagnosed as seizures. Sleep disturbance was present in all 16 patients and 7 of the 16 had daytime somnolence which resolved with dopaminergic medications. To our knowledge this is the first clinical series of moderate to severe PLMS in children and adolescents to be fully described in the literature.

A clinical and polysomnographic comparison of neuroleptic-induced akathisia and the idiopathic restless legs syndrome.

Neuroleptic-induced akathisia (NIA) is motor restlessness caused by dopamine receptor blocking antipsychotic agents. Nine patients with NIA and 11 patients with idiopathic restless legs syndrome (RLS) were studied polysomnographically. The sleep disturbances were milder in NIA than idiopathic RLS but increased numbers of awakenings and decreased sleep efficiencies were common to both groups. In addition, RLS patients demonstrated prolonged sleep latencies. Periodic movements in sleep (PMS) were present in only 5 of 9 patients with NIA but in all 11 patients with idiopathic RLS. In no NIA patient did we see the multiple, large amplitude, violent, resting myoclonic jerks of the legs that we saw during wakefulness in some of our more severe cases of idiopathic RLS. NIA patients tended to experience inner restlessness and idiopathic RLS patients tended to experience leg paresthesias as an antecedent to motor restlessness. Idiopathic RLS patients had symptoms that were worse at night and in repose far more frequently than patients with NIA. NIA and idiopathic RLS have similarities and differences. Because both NIA and idiopathic RLS are characterized by motor restlessness and sleep disturbances, the pharmacodynamics of antipsychotic medications may give clues as to both the cause and treatment of idiopathic RLS.

Randomized, Double-Blind, Placebo-Controlled Study of Clonidine in Restless Legs Syndrome.

Ten patients with idiopathic restless leg syndrome (RLS) were asked to rate their symptoms at baseline during 2 weeks of placebo and 2 weeks of clonidine treatment by using a four-point scale. On two consecutive nights of each treatment period, polysomnography (PSG) and actigraphic studies were performed. Patients subjectively reported improvement in leg sensations (p = 0.02) and motor restlessness (p = 0.001) while receiving clonidine (mean = 0.5 mg/day). On PSG testing, sleep onset occurred faster with clonidine (12 minutes) compared with placebo (30 minutes) and baseline (47 minutes) (p = 0.006). Adverse findings associated with clonidine treatment included decreased percent REM sleep in the clonidine group (4%) compared with placebo (16%) and baseline (16%) (p = 0.001) and increased REM latency in the clonidine group (195 minutes) compared to the placebo (70 minutes) and baseline groups (89 minutes) (p = 0.028). There were no significant changes in total sleep time, stage 1 and 2 sleep, sleep efficiency, awakenings, arousals or periodic limb movements in sleep. There was a nonstatistical trend toward and increase in stage 3 and 4 sleep and a decrease in motor activity as measured by actigraphic recordings. Globally, seven out of 10 patients felt clonidine was more effective than placebo. Four patients chose to continue clonidine after the study. Clonidine may be an effective treatment for RLS patients who don't have large numbers of sleep-disrupting periodic limb movements but have delayed sleep onset due to leg sensations and subsequent motor restlessness.

Successful treatment of the idiopathic restless legs syndrome in a randomized double-blind trial of oxycodone versus placebo.

In a double-blind randomized crossover trial, oxycodone or placebo was given in divided night-time doses to 11 patients with idiopathic restless legs syndrome (RLS) for 2 weeks prior to appropriate polysomnographic studies. Under double-blinded conditions, patients were asked to do daily ratings of their leg sensations, motor restlessness and daytime alertness on a 1-4 scale for the 2 weeks prior to the polysomnographic studies and for the nights of the polysomnographic studies as well. Leg sensations (p < 0.009), motor restlessness (p < 0.006) and daytime alertness (p < 0.03) were significantly improved on oxycodone as compared to baseline or placebo. Patients were studied polysomnographically under double-blinded conditions for 2 nights in each phase of the protocol. On an average dose of 15.9 mg oxycodone (equivalent to approximately three 5-mg tablets of commercial preparation), there was a statistically significant reduction in the number of periodic limb movements in sleep [(PLMS)/hour sleep (p < 0.004)] and in the number of arousals/hour sleep (p < 0.009) on drugs as compared to baseline or placebo. A statistically significant improvement was also noted in sleep efficiency (p < 0.006) and 10 of the 11 patients preferred oxycodone over placebo. We conclude that oxycodone is an effective treatment for RLS and PLMS.

Circadian rhythm of motor restlessness and sensory symptoms in the idiopathic restless legs syndrome.

STUDY OBJECTIVES: To determine if motor restlessness in the Restless Legs Syndrome (RLS) shows a circadian rhythm with maximum at night, as previously found for subjective discomfort and periodic limb movements (PLMs), and to correlate RLS peak intensity with the core temperature cycle. DESIGN: Subjects underwent two days of normally timed wakefulness and sleep followed by a night and subsequent day of sleep deprivation. Activity was standardized through modified suggested immobilization tests (mSITs). SETTING: The study was conducted in a laboratory environment with a bedroom equipped for polysomnography during sleep and the mSITs. PATIENTS: Nine patients (mean age 59.8+/-11.3 years [range: 33-72]; 4 males, 5 females) with clinically severe idiopathic RLS. INTERVENTIONS: Patients were monitored with continuous ambulatory activity and core temperature recording. The mSITs were performed every three hours while subjects were awake. During the mSITs, subjective discomfort was measured every 15 minutes while motor restlessness was assessed through activity monitoring. MEASUREMENTS AND RESULTS: Subjective discomfort and motor restlessness increased from a trough in the morning to a maximum at night in the hours following midnight. Peak intensity was found on the falling phase of the core temperature cycle, whose circadian rhythm appeared to be within the normal range for age. CONCLUSIONS: An independent circadian factor modulates the intensity of RLS, which seems to peak on the falling phase of the core temperature cycle. Therefore, the diagnostic criteria that RLS occurs with rest and during the night have independent bases. Furthermore, RLS may be partially controlled by some process or substance whose level varies with the normal circadian rhythm.

Consistencies and inconsistencies underlying the quantitative assessment of leukemia risk from benzene exposure.

This paper examines recent risk assessments for benzene and observes a number of inconsistencies within the study and consistencies between studies that should effect the quantitative determination of the risk from benzene exposure. Comparisons across studies show that only acute myeloid leukemia (AML) is found to be consistently in excess with significant benzene exposure. The data from the Pliofilm study that forms the basis of most quantitative assessments reveal that all the AML cases came from only one of the three studied plants and that all the benzene exposure data came from the other plants. Hematological data from the 1940s from the plant from which almost all of the industrial hygiene exposure data come do not correlate well with the originally published exposure estimates but do correlate well with an alternative set of exposure estimates that are much greater than those estimates originally published. Temporal relationships within the study are not consistent with those of other studies. The dose-response relationship is strongly nonlinear. Other data suggest that the leukemogenic effect of benzene is nonlinear and may derive from a threshold toxicity.

Opioid treatment of periodic movements in sleep in patients without restless legs.

Opioids may be a useful treatment for some patients with Periodic Movements of Sleep (PMS) and sleep disturbances. Four patients who had only idiopathic PMS and sleep disturbances but not Restless Legs Syndrome (RLS) were treated with various opioids. Two of the patients responded with a more than 98% decrease in the number of PMS per night of sleep and a doubling of the percentage of sleep period time spent in deep (Stages 3 and 4) sleep.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration to C57-black mice leads to parallel decrements in neostriatal dopamine content and tyrosine hydroxylase activity.

The administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to C57-black mice (4 doses of 20 mg/kg, at 2 h intervals) led to a large decrement in the neostriatal content of dopamine (92%) and a parallel decrease in tyrosine hydroxylase activity (91%). MPTP administration also caused highly significant but lesser decrements in the neostriatal content of dihydroxyphenylacetic acid (84%) and homovanillic acid (68%). These data are consistent with other observations which suggest that MPTP administration to mice results in a destruction of the dopaminergic nigrostriatal pathway.

A blinded study of the suppressibility of involuntary movements in Huntington's chorea, tardive dyskinesia, and L-dopa-induced chorea.

Videotapes of patients with Huntington's chorea, tardive dyskinesia (TD), and L-DOPA-induced chorea in Parkinson's disease were taken while the patients were seated with their legs dangling. The videotapes were scored in a blinded fashion for suppressibility of dyskinesias. Most patients with TD or L-DOPA-induced chorea substantially suppressed their involuntary movements, whereas most patients with Huntington's chorea did not. There was a small overlap between the TD and Huntington's chorea groups and suppressibility therefore could not absolutely distinguish between them. Suppressibility testing may nonetheless be a valuable clinical tool since a good, excellent, or complete suppressibility rating was highly suggestive of TD but not Huntington's chorea. TD and L-DOPA-induced chorea may be more pathophysiologically similar to each other than either is to Huntington's chorea.

A case report of naltrexone treatment of self-injury and social withdrawal in autism.

The endogenous opiate release theory of self-injurious behavior (SIB) was investigated through double-blind placebo-controlled administration of naltrexone hydrochloride (Trexan) to a 14-year-old autistic and mentally retarded male for treatment of severe SIB. Results yielded a marked decrease in SIB during two phases of active drug treatment, though SIB did not revert to originally observed placebo levels during a second placebo phase. An increase in social relatedness also was observed during phases of active drug treatment. Opiate theories of self-injury and the possible interrelationship of self-injury with pituitary-adrenal arousal and with social relatedness are discussed.

Periodic limb movements and restless legs syndrome.

The criteria that characterize restless legs syndrome (RLS) and the differential diagnoses are discussed. Clinical signs include sleep disturbance, involuntary movements in sleep or wakefulness, a normal neurologic examination, a chronic clinical course, and, in some cases, a positive family history. Periodic limb movements during sleep, which also may occur as an isolated finding, may or may not cause frequent arousals or awakenings. Clinical diagnosis of idiopathic or symptomatic forms of RLS can be supported with polysomnography. Treatment of first choice consists of dopaminergic drugs or dopamine agonist followed by opioids or benzodiazepines.

Periodic limb movement disorder and restless legs syndrome in children with attention-deficit hyperactivity disorder.

Sleep disruption can lead to symptoms of attention-deficit hyperactivity disorder (ADHD) in children. Since periodic limb movement disorder and/or restless legs syndrome can cause sleep disruption, we assessed whether these two specific sleep disorders are likely to occur in children with ADHD. We asked a series of 69 consecutive parents of children with ADHD questions about the symptoms of periodic limb movement disorder. Based on a positive response to these periodic limb movement disorder queries, 27 children underwent all-night polysomnography. Eighteen children (aged 2 to 15 years) of the 27 (26% of the 69 children with ADHD) had 5 or more periodic leg movements in sleep per hour of sleep and had complaints of sleep disruption, thus fulfilling the criteria for periodic limb movement disorder. A comparably age- and sex-matched group of children referred to a sleep laboratory for sleep complaints but without ADHD showed only a 5% prevalence (2 of 38 subjects) of periodic leg movements in sleep (P=.017). Eight of the 18 children with ADHD and periodic limb movement disorder and one of the two control patients with periodic limb movement disorder had both a personal and parental history of restless legs syndrome symptomatology. This study further documents the occurrence of periodic limb movement disorder and restless legs syndrome in children and is the first large-scale study establishing a possible comorbidity between ADHD and periodic limb movement disorder. We propose that the sleep disruption associated with periodic limb movement disorder and restless legs syndrome and the motor restlessness of restless legs syndrome while awake could contribute to the inattention and hyperactivity seen in a subgroup of ADHD-diagnosed children.

Dopaminergic therapy in children with restless legs/periodic limb movements in sleep and ADHD. Dopaminergic Therapy Study Group.

The long-term effects of monotherapy with levodopa or the dopamine agonist pergolide on the motor/sensory, behavioral, and cognitive variables in seven children with restless legs syndrome/periodic limb movements in sleep (RLS/PLMS) and attention-deficit-hyperactivity disorder (ADHD) were investigated. Five of the seven children had previously been treated with stimulants that had either been determined to be ineffective or to have intolerable side effects. Dopaminergic therapy improved the symptoms of RLS and reduced the number of PLMS per hour of sleep (P = 0.018) and associated arousals (P = 0.042) for the entire group. After treatment, three children no longer met the criteria for ADHD, and three reverted to normal on the Test of Variable Attention. ADHD improved in all seven as measured by the Connors parent rating scale (P<0.04) and the Child Behavior Checklist (P<0.05). A significant improvement also occurred in the visual, but not verbal, memory scores on the Wide Range Assessment of Memory and Learning (P<0.001). Five of seven children continue on dopaminergic therapy 3 years after treatment initiation, with good response. We postulate that the improvement in ADHD may be the result of the amelioration of RLS/PLMS and its associated sleep disturbance. Alternatively, ADHD and RLS/PLMS may share a common dopaminergic deficit.

Restless legs syndrome in childhood and adolescence.

Restless legs syndrome (RLS) is believed to be a condition primarily of middle to older age. However, it can have its onset in childhood. Five illustrative case histories with an autosomal dominant mode of inheritance are described. A mother and her 3 children (age: 6 1/2, 4 and 1 1/2 years) as well as a 16-year-old patient from a second family have typical RLS signs of leg discomfort (paresthesias) and motor restlessness prevalent at night and at rest, with temporary relief by activity. Polysomnography or videotaping revealed periodic limb movements in sleep (PLMS) and, in some cases, involuntary jerking of the legs was present during wakefulness as well. Clinicians should be aware that RLS can occur in childhood and adolescence and may be more common than heretofore recognized. "Growing pains" and attention deficit hyperactivity disorder (ADHD) are in the differential diagnosis of RLS in childhood.

HIV prevention in street youth.

Homeless adolescents have remained an underserved population throughout the human immunodeficiency/acquired immune deficiency syndrome epidemic. This article reviews the recent literature investigating human immunodeficiency virus (HIV) risk behavior among street youth. Prevalence rates of both adolescent homelessness and HIV seropositivity are unknown. However, data from a number of samples document a high prevalence of HIV risk behavior, sexually transmitted diseases, and alcohol/drug use among homeless adolescents. A number of individual and social factors, often associated with street survival, propel adolescents toward high-risk behavior. For some adolescents, testing HIV positive is perceived as advantageous in the procurement of basic needs such as food and shelter. HIV risk-reduction interventions must take into consideration the cause of homelessness, access to and participation in shelter services, and individual factors (such as the effects of sexual orientation and ethnicity) that frequently have not been systematically included in previous research. HIV risk for many homeless adolescents stems directly from their state of homelessness. National policies and funding are needed to address the health needs of these youth.

Opioids a better treatment for acute than tardive akathisia: possible role for the endogenous opiate system in neuroleptic-induced akathisia.

Patients who are on neuroleptics with acute akathisia improve more with opioid therapy than patients who are off neuroleptics with tardive akathisia. Since tardive akathisia usually occurs after long term neuroleptic exposure, we propose that this difference in therapeutic response is due to permanent changes in receptor sensitivity that arise from such prolonged exposure. We have previously described a patient with severe acute akathisia whose motor restlessness was totally suppressed by opioid therapy. This improvement was rapidly reversed by the opiate receptor blocker naloxone. This suggests that the endogenous opiate system is involved in the pathogenesis of neuroleptic-induced akathisia.

How sleep deprivation affects psychological variables related to college students' cognitive performance.

The effects of sleep deprivation on cognitive performance psychological variables related to cognitive performance were studied in 44 college students. Participants completed the Watson-Glaser Critical Thinking Appraisal after either 24 hours of sleep deprivation or approximately 8 hours of sleep. After completing the cognitive task, the participants completed 2 questionnaires, one assessing self-reported effort, concentration, and estimated performance, the other assessing off-task cognitions. As expected, sleep-deprived participants performed significantly worse than the nondeprived participants on the cognitive task. However, the sleep-deprived participants rated their concentration and effort higher than the nondeprived participants did. In addition, the sleep-deprived participants rated their estimated performance significantly higher than the nondeprived participants did. The findings indicate that college students are not aware of the extent to which sleep deprivation negatively affects their ability to complete cognitive tasks.

Social relatedness and autism: current research, issues, directions.

Social relatedness has recently become a primary focus of investigators in the field of autism. This shift to regarding disturbances in social relatedness as one of the defining manifestations of the disorder marks the movement of research on autistic disorder back to its origins, when Kanner first noted the "social and affective" symptoms of autism as pathognomonic. Currently, social impairment in autism is viewed as more pervasively characteristic of the disorder than any other single symptom. Further, there has been a recent proliferation of research designed to document the nature of social deficit in autism, and whether it is primarily affective, communicative, or cognitive in nature, or involves some combination of these three variables. This review summarizes recent research focusing on social relatedness in autism and discusses the implications of these findings.