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Restless legs with antiepileptic drug therapy.

The restless legs syndrome is generally benign but is occasionally associated with anemia, metabolic disorder, or polyneuropathy. Leg restlessness with disruptive nocturnal myoclonus has been described as a sleep disorder. We report two patients with complex partial and secondarily generalized seizures, who developed restless legs while taking methsuximide and phenytoin. They had no evidence of metabolic disturbance or neuromuscular disease, although one patient had fragmented sleep and disruptive myoclonus on polysomnography, and leg restlessness subsided with change of antiepileptic drugs. These symptoms could reflect transient alteration in peripheral nerve function not evident by examination or electrophysiologic studies, sleep disturbance by antiepileptic drugs or the effects of temporal lobe seizure foci on perception of the physiologic state of nerves and muscles.

Adult↗

The effects of dietary iron deprivation on murine circadian sleep architecture.

OBJECTIVES: Iron deficiency is considered a putative cause for restless legs syndrome (RLS), a human sensorimotor disorder characterized by a circadian presentation of symptoms during the evening hours that disrupts one's ability to sleep. We sought to evaluate the sleep-wake effects of diet-induced iron deficiency in mice as an animal model of RLS. To this end, we hypothesized that the iron-deprived mice would exhibit a sleep-wake circadian pattern characteristic of the human syndrome: increased wakefulness during the hours immediately preceding the sleep-predominant period. METHODS: Following weaning at post-natal day (PND) 21, C57BL/6J mice were assigned to one of two dietary treatments: iron-deficient (ID, n=7) or iron-adequate (i.e., control, CTL, n=6). At PND 44, the mice were surgically instrumented for polysomnographic (PSG) recording, and data were collected at young adulthood: PNDs 59 and 60. Sleep-wake architecture was characterized for the 12-h light and dark periods and also for six consecutive 4-h blocks comprising a 24-h day. RESULTS: The ID mice showed marked increases in wake time in the 4-h period prior to lights-on; both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep were reduced. In contrast, sleep-wake activity did not differ across the 12-h light period. CONCLUSIONS: Dietary iron deficiency in mice elicited increases in wakefulness during a particular circadian time point that corresponds to the period during which RLS symptoms would maximally disturb sleep onset and progression in humans. These data indicate that iron-deficient mice may provide a potentially useful animal model for RLS.

Animals↗

Restless legs syndrome: confirmation of linkage to chromosome 12q, genetic heterogeneity, and evidence of complexity.

BACKGROUND: Genes are involved in the etiology of restless legs syndrome, a common sensorimotor disorder. OBJECTIVES: To replicate and to further characterize our previously reported chromosome 12q linkage results. DESIGN: Family linkage study. SETTING AND PARTICIPANTS: A total of 276 individuals from 19 families have been examined using a selection of markers spanning the identified candidate interval on chromosome 12q. RESULTS: Two-point analyses of individual pedigrees indicated that 5 kindreds were consistent with linkage to chromosome 12q. When considering these 5 pedigrees along with the family in which linkage was originally reported, we observed a maximum 2-point logarithm-of-odds score of 5.67 (at theta = 0.10; for marker D12S1636; autosomal recessive) and a maximum multipoint logarithm-of-odds score of 8.84 between the interval defined by markers D12S326 and D12S304. Furthermore, our results also suggest the presence of heterogeneity in restless legs syndrome as linkage was formally excluded across the region in 6 pedigrees. Interestingly, significantly higher periodic leg movements during sleep indices were observed for all probands with restless legs syndrome from linked families. CONCLUSIONS: These results support the presence of a major restless legs syndrome-susceptibility locus on chromosome 12q, which has been designated as RLS1, and also suggest that at least one additional locus may be involved in the origin of this prevalent condition.

Chromosome Mapping↗

The prevalence of symptoms in end-stage renal disease: a systematic review.

Symptoms in end-stage renal disease (ESRD) are underrecognized. Prevalence studies have focused on single symptoms rather than on the whole range of symptoms experienced. This systematic review aimed to describe prevalence of all symptoms, to better understand total symptom burden. Extensive database, "gray literature," and hand searches were undertaken, by predefined protocol, for studies reporting symptom prevalence in ESRD populations on dialysis, discontinuing dialysis, or without dialysis. Prevalence data were extracted, study quality assessed by use of established criteria, and studies contrasted/combined to show weighted mean prevalence and range. Fifty-nine studies in dialysis patients, one in patients discontinuing dialysis, and none in patients without dialysis met the inclusion criteria. For the following symptoms, weighted mean prevalence (and range) were fatigue/tiredness 71% (12% to 97%), pruritus 55% (10% to 77%), constipation 53% (8% to 57%), anorexia 49% (25% to 61%), pain 47% (8% to 82%), sleep disturbance 44% (20% to 83%), anxiety 38% (12% to 52%), dyspnea 35% (11% to 55%), nausea 33% (15% to 48%), restless legs 30% (8%to 52%), and depression 27% (5%to 58%). Prevalence variations related to differences in symptom definition, period of prevalence, and level of severity reported. ESRD patients on dialysis experience multiple symptoms, with pain, fatigue, pruritus, and constipation in more than 1 in 2 patients. In patients discontinuing dialysis, evidence is more limited, but it suggests they too have significant symptom burden. No evidence is available on symptom prevalence in ESRD patients managed conservatively (without dialysis). The need for greater recognition of and research into symptom prevalence and causes, and interventions to alleviate them, is urgent.

Adult↗

A secondary analysis of racial differences in periodic leg movements in sleep and ferritin in hemodialysis patients.

BACKGROUND AND OBJECTIVE: Hemodialysis (HD) is associated with restless legs syndrome (RLS) and periodic leg movements in sleep (PLMS), but the mechanisms underlying these relationships remain unclear. African-American HD patients have been reported previously to have a reduced likelihood of RLS. Alterations in iron metabolism, known to be a risk factor for idiopathic forms of RLS, could represent the basis for these racial differences. PATIENTS AND METHODS: In secondary data analyses from a previously published study, we examined raw and log-transformed values for plasma ferritin and polysomnographically recorded PLMS in Caucasian and African-American HD patients. RESULTS: African-American (n=36) HD patients had higher ferritin and lower PLMS than Caucasians (n=10). However, within the African-American population, ferritin levels were unrelated to PLMS. CONCLUSIONS: These results are compatible with previously reported racial differences in RLS to the extent that PLMS were less common in the African-American population. However, they suggest that if a differential genetic vulnerability underlies those racial differences, it may not manifest as a deficiency in iron metabolism, at least within the constraints of the marker of iron stores used here (e.g. serum ferritin) and in the specific population studied (hemodialysis). Future studies with larger, more representative samples of African-Americans and Caucasians will be required to replicate such differences.

Adult↗

[Children exposed to "earth rays" are not more frequently ill than other children].

From time to time newspapers bring reports on "earth rays" and their alleged damaging effects on health. There is, however, no objective evidence which suggests the existence of earth rays. In spite of this, dowsers claim that earth rays are a main cause of disease, also in children. In this study we wanted to evaluate, using a double-blind design, the alleged effects of earth rays on young children. A total of 44 children in four nursery schools in the Bergen area were recruited. Two dowsers and one interviewer visited the homes of all the children. The dowsers evaluated the presence of earth rays over the child's bed while the parents were interviewed in an independent procedure about the child's medical history over the past 12 months. Whether or not earth rays where found over the child's bed, there where no differences in the reported health of the child with regard to upper and lower respiratory tract infections, stomach aches, allergies or sleeping habits. Parents' report on restlessness and hyperactivity were also the same. The study failed to find any health effects, adverse or not, of earth rays.

Background Radiation↗

[Psychophysiologic insomnia and periodic leg movements in sleep syndrome].

In 31 patients with psychophysiological insomnia, the relationship between periodic leg movements and sleep was studied. Patients with frequent periodic leg movements estimated their sleep latency to be longer than did patients with few or without leg movements. There were no other significant differences regarding sleep structure and subjective sleep quality between both groups. It appears likely that frequent periodic leg movements in patients with psychophysiological insomnia (not suffering from a restless legs syndrome) can be considered an accidental finding rather than an important factor involved in the pathogenesis of the disorder.

Arousal↗

Effects of exercise on sleep.

Historically, perhaps no daytime behavior has been more closely associated with better sleep than exercise. The assumption that exercise promotes sleep has also been central to various hypotheses about the functions of sleep. Hypotheses that sleep serves an energy conservation function, a body tissue restitution function, or a temperature down-regulation function all have predicted a uniquely potent effect of exercise on sleep because no other stimulus elicits greater depletion of energy stores, tissue breakdown, or elevation of body temperature, respectively. Exercise offers a potentially attractive alternative or adjuvant treatment for insomnia. Sleeping pills have a number of adverse side effects and are not recommended for long-term use, partly on the basis of a significant epidemiologic association of chronic hypnotic use with mortality. Other behavioral/cognitive treatments are more effective for chronic insomnia treatment, but difficult and costly to deliver. By contrast, exercise could be a healthy, safe, inexpensive, and simple means of improving sleep.

Anxiety↗

Sleep-related non-epileptic motor phenomena.

We describe the clinical, neurophysiological and polysomnographic characteristics of some involuntary motor nocturnal events occurring during sleep or at the transition from wakefulness to sleep.

Brain↗

Parents' and children's ratings of sleep behavior, excitement, and tiredness: a 10-week longitudinal study.

In a 10-week longitudinal study, 29 parents and their children kept daily records of the children's sleep behaviors, excitement levels, and tiredness levels. Although the hypothesized increase in sleep behaviors such as sleepwalking and restlessness during the week of Christmas did not occur, children rated as more excitable by their parents and themselves exhibited a higher frequency of sleep behaviors. Positive associations were also found between averaged tiredness ratings and sleep scores. The results support previous findings of an association between arousal characteristics of children and their sleep behavior. Moderate validity coefficients were obtained for parents' and children's ratings of excitement, tiredness, and nocturnal waking.

Arousal↗

Sleep disorders in Parkinson's disease: epidemiology and management.

Sleep problems are an under-emphasised cause of disability in Parkinson's disease (PD) and may be seen independently of PD, associated with primary PD pathology, or as a result of antiparkinsonian medications. Common sleep disorders include excessive daytime sleepiness, rapid eye movement (REM) sleep behaviour disorder, night-time wakefulness and restless legs syndrome. A number of strategies may be used to improve sleep cycle disturbances, and often these interventions do not require pharmacological manipulation. Restoring traditional mealtimes and scheduling activities during predicted periods of sleepiness may help alleviate daytime somnolence; the use of controlled-release levodopa preparations or administration of a catechol-O-methyl transferase (COMT) inhibitor with levodopa at bedtime may reduce periods of night-time wakefulness. Administration of clonazepam at bedtime may assist with REM sleep behaviour disorder but, because this agent can result in daytime somnolence, experimentation with dosage times is recommended. Sleep attacks are described as a sudden, unavoidable transition from wakefulness to sleep and, although rare, have been described with pramipexole, ropinirole and other dopamine agonists. Although the condition has yet to be recognised by the International Association of Sleep Disorders, patients with PD who report rapid sleep onset should be evaluated for the possibility of sleep attacks. If sleep attacks are suspected, it is reasonable to strongly caution patients regarding potentially risk-associated activities such as driving, and to consider careful withdrawal of dopaminergic therapy.

Antiparkinson Agents↗

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.

Adult↗