Wayne A. Hening

Restless legs syndrome: diagnostic criteria, special considerations, and epidemiology. A report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health.

BACKGROUND Restless legs syndrome is a common yet frequently undiagnosed sensorimotor disorder. In 1995, the International Restless Legs Syndrome Study Group developed standardized criteria for the diagnosis of restless legs syndrome. Since that time, additional scientific scrutiny and clinical experience have led to a better understanding of the condition. Modification of the criteria is now necessary to better reflect that increased body of knowledge, as well as to clarify slight confusion with the wording of the original criteria. SETTING The restless legs syndrome diagnostic criteria and epidemiology workshop at the National Institutes of Health. PARTICIPANTS Members of the International Restless Legs Syndrome Study Group and authorities on epidemiology and the design of questionnaires and scales. OBJECTIVE To modify the current criteria for the diagnosis of restless legs syndrome, to develop new criteria for the diagnosis of restless legs syndrome in the cognitively impaired elderly and in children, to create standardized criteria for the identification of augmentation, and to establish consistent questions for use in epidemiology studies. RESULTS The essential diagnostic criteria for restless legs syndrome were developed and approved by workshop participants and the executive committee of the International Restless Legs Syndrome Study Group. Criteria were also developed and approved for the additional aforementioned groups.

An Algorithm for the Management of Restless Legs Syndrome

Restless legs syndrome (RLS) is a common disorder with a prevalence of 5% to 15%. Primary care physicians must become familiar with management of this disorder. This algorithm for the management of RLS was written by members of the Medical Advisory Board of the Restless Legs Syndrome Foundation and is based on scientific evidence and expert opinion. Restless legs syndrome is divided into intermittent, daily, and refractory types. Nonpharmacological approaches, including mental alerting activities, avoiding substances or medications that may exacerbate RLS, and addressing the possibility of iron deficiency, are discussed. The role of carbidopa/levodopa, dopamine agonists, opioids, benzodiazepines, and anticonvulsants for the different types of the disorder is delineated.

Further studies on periodic limb movement disorder and restless legs syndrome in children with attention-deficit hyperactivity disorder

Fourteen consecutive children who were newly diagnosed with attention‐deficit hyperactivity disorder (ADHD) and who had never been exposed to stimulants and 10 control children without ADHD underwent polysomnographic studies to quantify Periodic Limb Movements in Sleep (PLMS) and arousals. Parents commonly gave both false‐negative and false‐positive reports of PLMS in their children, and a sleep study was necessary to confirm their presence or absence. The prevalence of PLMS on polysomnography was higher in the children with ADHD than in the control subjects. Nine of 14 (64%) children with ADHD had PLMS at a rate of >5 per hour of sleep compared with none of the control children (p <0.0015). Three of 14 children with ADHD (21%) had PLMS at a rate of >20 per hour of sleep. Many of the PLMS in the children with ADHD were associated with arousals. Historical sleep times were less for children with ADHD. The children with ADHD who had PLMS chronically got 43 minutes less sleep at home than the control subjects (p = 0.0091). All nine children with ADHD who had a PLMS index of >5 per hour of sleep had a long‐standing clinical history of sleep onset problems (>30 minutes) and/or maintenance problems (more than two full awakenings nightly) thus meeting the criteria for Periodic Limb Movement Disorder (PLMD). None of the control children had a clinical history of sleep onset or maintenance problems. The parents of the children with ADHD were more likely to have restless legs syndrome (RLS) than the parents of the control children. Twenty‐five of 28 biologic parents of the children with ADHD and all of the biologic parents of the control children were reached for interview. Eight of twenty‐five parents of the children with ADHD (32%) had symptoms of RLS as opposed to none of the control parents (p = 0.011). PLMS may directly lead to symptoms of ADHD through the mechanism of sleep disruption. Alternative explanations for the association between ADHD and RLS/PLMS are that they are genetically linked, they share a common dopaminergic deficit, or both.

Long-term follow-up on restless legs syndrome patients treated with opioids.

The medical records of 493 patients with restless legs syndrome (RLS) from three major centers were studied to determine the number and outcome of patients who had been treated with opioids as a monotherapy. At one time or another 113 patients (51 men, 62 women; age range, 37–88 years) had been on opioid therapy either alone (36 patients) or with opioids added secondarily to other medications used to treat RLS (77 patients). Twenty‐three of the 36 opioid monotherapy patients had failed dopaminergic and other therapeutic agents prior to the initiation of opioid monotherapy. Twenty of the 36 opioid monotherapy patients continue on monotherapy for an average of 5 years 11 months (range, 1–23 years), despite their knowledge of the availability of other therapies. Of the 16 patients who discontinued opioids as a sole therapy, the medication was discontinued in only one case because of problems related to addiction and tolerance. Polysomnography on seven patients performed after an average of 7 years 1 month of opioid monotherapy (range, 1–15 years) showed a tendency toward an improvement in all leg parameters and associated arousals (decrease in PLMS index, PLMS arousal index, and PLM while awake index) as well as all sleep parameters (increase in stages 3 and 4 and REM sleep, total sleep time, sleep efficiency, and decrease in sleep latency). Two of these seven patients developed sleep apnea and a third patient had worsening of preexisting apnea. Opioids seem to have long‐term effectiveness in the treatment of RLS and PLMS, but patients on long‐term opioid therapy should be clinically or polysomnographically monitored periodically for the development of sleep apnea.

Dyskinesias while awake and periodic movements in sleep in restless legs syndrome Treatment with opioids

In five unrelated patients with the restless legs syndrome, opioid drugs relieved restlessness, dysesthesias, dyskinesias while awake, periodic movements of sleep, and sleep disturbances. When naloxone was given parenterally to two treated patients, the signs and symptoms of the restless legs syndrome reappeared. Naloxone placebo had no effect. Opioid medications may offer a useful therapy for the restless legs syndrome. The endogenous opiate system may be involved in the pathogenesis of the syndrome.

Control of voluntary and reflexive saccades in Parkinson’s disease

Abstract Eight patients with idiopathic Parkinson’s disease (PD) were compared with a group of age-matched controls on both reflexive saccade and antisaccade tasks. While reflexive, visually guided saccades led to equivalent performance in both groups, PD patients were slower, made more errors, and showed reduced gain on antisaccades (AS). This is consistent with previous results showing that PD patients have no difficulty with reflexive saccades but show deficiencies in a number of voluntary saccade paradigms. Moreover, visual information in the form of landmarks improves AS performance more for PD patients than controls, a finding analogous to results seen with other motor acts such as target-directed pointing. Results are discussed in terms of a two-process model of attention and eye movements.

Beyond Benzodiazepines: Alternative Pharmacologic Agents for the Treatment of Insomnia

OBJECTIVE: To review the epidemiology, etiology, and classification of insomnia and provide an overview of the pharmacologic therapy of insomnia. Novel nonbenzodiazepine hypnotics including zolpidem, zopiclone, and zaleplon, as well as nonprescription products such as valerian and melatonin, are reviewed in detail. DATA SOURCES: A MEDLINE search was performed to identify relevant clinical studies, case reports, abstracts, and review articles published between April 1992 and December 1997. Key search terms included insomnia, benzodiazepines, zolpidem, zopiclone, zaleplon, Cl 284,846, melatonin, and valerian. Additional references were obtained from the lists of review articles and textbooks. DATA EXTRACTION AND SYNTHESIS: Data concerning the safety and efficacy of the hypnotic agents were extracted from all available clinical trials and abstracts. Background information regarding insomnia, benzodiazepines, and other hypnotics was extracted from the most current literature, including review articles and textbooks. CONCLUSIONS: New developments in benzodiazepine receptor pharmacology have introduced novel nonbenzodiazepine hypnotics that provide comparable efficacy to benzodiazepines. Although they may possess theoretical advantages over benzodiazepines based on their unique pharmacologic profiles, they offer few, if any, significant advantages in terms of adverse effects. Over-the-counter agents such as valerian and melatonin may be useful in alleviating mild, short-term insomnia, but further clinical trials are required to fully evaluate their safety and efficacy.

Definition of restless legs syndrome, how to diagnose it, and how to differentiate it from RLS mimics

Restless legs syndrome (RLS) is a clinical diagnosis based primarily on self‐reports of individuals. The International RLS Study Group has published diagnostic criteria that are essential for an operational diagnosis of RLS; further clinical features are considered by the group supportive for or associated with RLS. However, sensitivity and specificity are not perfect and “mimics” of RLS have been reported, i.e., other conditions like nocturnal cramps sometimes can appear to fulfill the essential diagnostic criteria indicating the need for more thorough understanding of the diagnostic criteria and better differential diagnoses. To contribute to the accuracy of diagnostic processes in RLS, we recapitulate the definition of RLS as an urge to move focused on the legs (and arms in some patients). This urge to move often but not always occurs together with dysesthesia, i.e. unpleasant abnormal sensations appearing without any apparent sensory stimulation. The urge to move and any accompanying dysesthesia must be engendered by rest, relieved by movement and worse in the evening or night. Succinctly, RLS can be summarized in medical terminology as a “movement‐responsive quiescegenic nocturnal focal akathisia usually with dysesthesias.” Empirical approaches to investigate the independence of the essential criteria “worsening at night” and “worsening at rest” are reported. Possible differential diagnoses of RLS are discussed under the perspective of the NIH diagnostic criteria of RLS. Standardized methods to assess a RLS diagnosis are presented which might improve differential diagnosis and in general the reliability and validity of RLS diagnosis.

Organization of voluntary movement

There have recently been a number of advances in our knowledge of the organization of complex, multi-joint movements. Promising starts have been made in our understanding of how the motor system translates information about the location of external targets into motor commands encoded in a body-based coordinate system. Two simplifying strategies for trajectory control that are discussed are parallel specification of response features and the programming of equilibrium trajectories. New insights have also been gained into how neural systems process sensory information to plan and assist with task performance. A number of recent papers emphasize the feedforward use of sensory input, which is mediated through models of the external world, the bodys physical plant, and the task structure. These models exert their influence at both reflex and higher levels and permit the preparation of predictive default parameters of trajectories as well as strategies for resolving task demands.

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.