Periodic leg movements in sleep in essential hypertension

Abstract The presence of periodic leg movements in sleep (PLMS) was assessed in 91 subjects diagnosed with essential hypertension. More than 18 per cent of the sample had PLMS, which is considerably higher than in normal controls. Also, the prevalence was significantly correlated with the severity of hypertension, as well as with age. Periodic leg movements in sleep were more frequent in the first few hours of the sleep period and during sleep stages 1 and 2. The arousing effect of PLMS was minimal, with only 17 per cent of all events related to an EEG arousal. Our results suggest that PLMS are common in people with essential hypertension, although they do not seem to be associated with any particular sleep disorder.     

Periodic leg movements and REM sleep without atonia in Parkinson's disease with camptocormia

Camptocormia (a flexion of the trunk that only appears when standing or walking) affects a minority of patients with Parkinson's disease (PD). As it responds poorly to levodopa and is associated with reduced midbrain and pons volume, it may result from non‐dopaminergic, brainstem lesions. As several sleep abnormalities in PD also result from non‐dopaminergic brainstem lesions, we monitored sleep in 24 non‐demented PD patients with (n = 12) and without (n = 12) camptocormia and in 12 controls. Nearly half (42%) patients with camptocormia had abnormal periodic leg movement indices (>15/h), versus 17% patients without camptocormia and 8% of controls (p = 0.02). In addition, the percentage of enhanced muscle activity during REM sleep (measured on the chin and on the limb muscles) tended to be higher in patients with than without camptocormia (51 ± 39% vs. 20 ± 25%, p = 0.06). The other sleep and REM sleep characteristics (sleep and REM sleep onset latencies, sleep time and sleep stage percentages, REMs density, arousal, and apnea‐hypopnea indices) were not different between these two PD groups. Lesions causing this axial dystonia may spare the sleep systems but affect the control of movements during sleep. © 2009 Movement Disorder Society     

Antidepressants and periodic leg movements of sleep.

BACKGROUND: Frequent electroencephalographic arousals or awakenings associated with periodic leg movements (PLM) might be responsible in part for the complaints of sleep disturbances made by patients treated with antidepressants. Past studies, however, have determined the effects of only certain limited antidepressants, generally in small numbers of subjects, and never in a head-to-head study. METHODS: A total of 274 consecutive patients taking antidepressants and 69 control subjects not taking antidepressants met criteria among patients referred for overnight diagnostic polysomnography. Periodic leg movements were visually counted and the PLM index (PLMI) was calculated. RESULTS: The venlafaxine and selective serotonin reuptake inhibitor (SSRI) groups had significantly higher mean PLMIs than control and bupropion groups. Periodic leg movement indexes at thresholds considered to be of potential clinical significance were more statistically prevalent in the SSRI and venlafaxine groups compared with the control and bupropion groups. The odds ratio of having a PLMI greater than 20 was 5.15 for the SSRI group and 5.24 for the venlafaxine group compared with the control group. CONCLUSIONS: Venlafaxine and SSRI-induced PLM are likely to be the result of enhanced serotonergic availability and secondarily decreased dopaminergic effects. The results of this study might assist in the selection of antidepressants, especially in patients with pronounced sleep complaints.     

Effects of periodic leg movements during sleep in middle-aged subjects without sleep complaints.

Recent reports have called into question the relevance of periodic leg movements during sleep disorder (PLMSD) as a specific clinical entity. Because periodic leg movement in sleep index (PLMSI) increases with age, it has become an important exclusion criterion in research on aging. However, it is unknown if PLMSI is related to sleep quality in middle-aged subjects without sleep complaints. The sleep of 70 healthy, middle-aged subjects (age 40 to 60 years) without sleep complaints was evaluated. Subjects were divided into two groups according to their PLMSI severity: (1) 43 subjects (28 women, 15 men) were in the low PLMSI group (<5) and (2) 22 subjects (9 women, 13 men) were in the high PLMSI group (>10). A significantly higher proportion of men than women showed PLMSI greater than 5. There was no significant effect of PLMSI severity group for polysomnographic sleep parameters. PLMSI exerted a small but significant effect on subjective sleep quality, especially in middle-aged men. These results raise questions about the relevance of PLMSI as a pathological index for middle-aged subjects without sleep complaints and support the notion that an increase in PLMSI may be part of the normal process of aging associated with the loss of dopaminergic function.     

Periodic limb movements during sleep in alcohol dependent patients

Complaints of sleep disturbances are common among alcohol dependent patients during subacute abstinence. Recovered patients may show persistent sleep abnormalities for months or even years. In the present study we studied the issue whether periodic limb movements in sleep and disturbances of nocturnal respiration are more frequent in alcohol dependent patients than healthy subjects and may be of predictive value for sustained abstinence vs. relapse after withdrawal. Forty alcohol dependent patients spent three nights in the sleep laboratory at three time points: 2 to 3 weeks after withdrawal (T0) and at follow-up investigations 6 (T1) and 12 (T2) months after discharge from the hospital. Measurements of PLMS-arousal index and nocturnal respiration were performed during the first laboratory night of each measurement point. Alcohol dependent patients displayed a significantly enhanced PLMS-arousal index at T0 compared to age- and gender-matched healthy subjects, whereas no alterations of nocturnal respiration were found. The PLMS-arousal index at T0 was significantly elevated in patients who relapsed during the next 6 months compared to abstinent patients. In a discriminant function analysis the PLMS-arousal index classified 55 % of the patients correctly with respect to outcome after 6 months. It correctly predicted 80 % of abstainers and 44 % of the patients who relapsed. According to neurobiological models of the generation of PLMS and the etiopathology of alcohol dependence a genetically determined vulnerability of the dopaminergic system is discussed as a factor underlying an increased risk of relapse in a subgroup of alcohol dependent patients. Received: 14 November 2001 / Accepted: 7 May 2002     

Periodic leg movements in sleep in elderly patients with Parkinsonism and Alzheimer’s disease

Background: Periodic leg movements in sleep (PLMS) are non‐epileptiform, repetitive movements of the lower limbs that have been associated with apparent dopamine deficiency. We hypothesized that elderly patients with a disease characterized primarily by dopamine depletion (Parkinsonism) would have higher rates of PLMS than age‐matched controls or a different neurodegenerative condition not primarily involving a hypodopaminergic state, Alzheimer’s disease (AD). Methods: We compared rates of PLMS derived from in‐laboratory overnight polysomnography in patients with Parkinsonism (n = 79), AD (n = 28), and non‐neurologically impaired, community‐based controls (n = 187). Results: Patients with Parkinsonism not receiving levodopa had significantly higher rates of PLMS than did patients with Parkinsonism receiving levodopa as well as higher rates than seen in AD and controls. Other medications did not appear to exert the pronounced effect of levodopa on PLMS in this Parkinsonian patient population. The symptom of leg kicking was reported more frequently in Parkinsonism and was associated with higher rates of PLMS. Caregiver reported leg kicking was unrelated to PLMS in AD. Conclusions: Results are broadly compatible with a dopaminergic hypothesis for PLMS in Parkinsonism. The clinical significance of the negative findings in patients with AD requires further investigation.     

Narcoleptic canines display periodic leg movements during sleep.

Periodic leg movements during sleep (PLMS) is a high prevalent sleep disorder of unknown etiology. The disease is pharmacologically treated with dopaminergic agonists (i.e. D2/D3 agonists) and opiates. Periodic leg movements during sleep often occur in narcoleptic patients. We observed that narcoleptic canines, like narcoleptic humans, also exhibit jerky, unilateral or bilateral slow leg movements during sleep. The movements in dogs are characterized by repetitive dorsiflexions of the ankle, lasting 0.5-1.5 s, and occur at regular intervals of 3-20 s, thus showing similarities to PLMS in humans. The observation that D2/D3 agonists aggravate cataplexy in narcoleptic dogs suggests that altered dopaminergic regulation in canine narcolepsy may play a critical role in both cataplexy and PLMS. Our canines may therefore be an invaluable resource in PLMS research.     

Rapid eye movement dependent central apnea with periodic leg movements

Central sleep apnea is a period of at least 10 s without airflow, during which no ventilatory effort is present. Most of the central apneas occur in Non-Rapid eye movement (NREM) sleep. Central apnea occuring in Rapid eye movement (REM) sleep is extremely rare. We present our patient who had a diagnosis of obstructive sleep apnea in another sleep center since 2003. His Auto Continuous Positive Airway Pressure (CPAP) machine was disrupted so he admitted to our center to renew his machine and for daytime sleepiness while using his machine. The polysomnography revealed central apneas ending with respiratory arousals and periodic leg movements in rapid eye movement (REM) stage. We found no cause for central apneas. The patient benefited from servo ventilator therapy. We present this case as an unusual form of central apnea with the review of the literatures. Even the patients diagnosed as obstructive sleep apnea should be analyzed carefully. The diagnosis and the therapeutic approach may change in the favor of the patient.     

EEG-tomographic studies with LORETA on vigilance differences between narcolepsy patients and controls and subsequent double-blind,placebo-controlled studies with modafinil

Abstract The aim of the present study was to identify brain regions associated with vigilance in untreated and modafinil-treated narcoleptic patients by means of low-resolution brain electromagnetic tomography (LORETA). 16 drug-free narcoleptics and 16 normal controls were included in the baseline investigation. Subsequently patients participated in a double-blind, placebo-controlled crossover study receiving a three-week fixed titration of modafinil (200, 300, 400 mg) and placebo. Measurements comprised LORETA, the Multiple Sleep Latency Test (MSLT) and the Epworth Sleepiness Scale (ESS) obtained before and after three weeks therapy. Statistical overall analysis by means of the omnibus significance test demonstrated significant inter-group differences in the resting (R-EEG), but not in the vigilance-controlled recordings (V-EEG). Subsequent univariate analysis revealed a decrease in alpha-2 and beta 1–3 power in prefrontal, temporal and parietal cortices, with the right hemisphere slightly more involved in this vigilance decrement. Modafinil 400 mg/d as compared with placebo induced changes opposite to the aforementioned baseline differences (key-lock principle) with a preponderance in the left hemisphere. This increase in vigilance resulted in an improvement in the MSLT and the ESS. LORETA provided evidence of a functional deterioration of the fronto-temporo-parietal network of the right-hemispheric vigilance system in narcolepsy and a therapeutic effect of modafinil on the left hemisphere, which is less affected by the disease.     

Periodic leg movements are part of the B-wave rhythm and the cyclic alternating pattern

Periodic leg movements (PLM) in sleep are supposed to constitute a frequent cause of insomnia. There is some controversy whether PLM are the cause of insomnia by provoking microarousals or whether they are simply an epiphenomenon not causally related to the insomnia. We examined four patients with PLM by overnight polysomnography and concomitant transcranial Doppler sonography (TCD) monitoring, 13 patients with suspected normal pressure hydrocephalus by concomitant overnight polysomnography and intracranial pressure recording, and 10 healthy volunteers by concomitant overnight polysomnography and TCD monitoring. EEG arousals occurred more frequently before than after the PLM. PLM were associated with increase in heart rate, breathing amplitude, and cerebral blood flow velocity assessed by TCD. PLM occurred with a mean wavelength of 40.5 s. This mean wavelength corresponded to similar values calculated for intracranial pressure B-waves (43.3 s) in 13 patients with suspected normal-pressure hydrocephalus, TCD B-wave equivalents (42.2 s) in 10 healthy young adults and the frequency of the cyclic alternating pattern in EEg recordings (40 s). Our data suggest that these cyclic variations with a wavelength of about 40 s are part of a common endogenous rhythm. PLM seem to be an epiphenomenon of this rhythm and not the cause of insomnia.     

Bilateral leg movements during sleep: detailing their structure and features in normal controls and in patients with restless legs syndrome

ObjectiveThe aim of this study was to analyze statistically the number of single leg movements (LMs) forming bilateral LMs during sleep, along with their combined duration, to eventually provide evidence-based data for the adjustment of the current scoring rules defining bilateral LMs.MethodsPolysomnographic recordings of 111 untreated patients with RLS with a median age of 56.0 years, along with 42 normal controls with a mean age of 60.0 years, were included. In each recording, we identified all LMs that were considered as bilateral when two or more LMs were overlapping or the onset of the following movement was <0.5 second after the offset of the preceding LM. The remaining LMs were classified as monolateral. A series of parameters were computed for both bilateral and monolateral LMs.ResultsThe duration of monolateral LMs in RLS patients was significantly longer than that of normal controls. For bilateral LMs, the maximum number of single LMs forming a bilateral movement and the maximum duration were slightly higher in RLS patients; however, the distribution of the number of individual LMs forming a single bilateral LM was similar. Only 0.12% and 0.27% of bilateral LMs consisted of >4 individual movements, and only 0.16% and 1.90% of bilateral LMs were >15 seconds in RLS patients and healthy controls, respectively.ConclusionOur results strongly suggest that bilateral LMs during sleep should be constituted by no more than four individual LMs and should have a maximum duration of 15 seconds.     

Sleep-related leg movements in obstructive sleep apnea: definitions,determinants, and clinical consequences

Study objectivesTo investigate (1) the effect of different scoring rules on leg movement (LM) classification in patients with obstructive sleep apnea (OSA); (2) determinants of respiratory event related leg movements (rLM); and (3) to relate LM parameters to clinical outcomes.Methods(1) LM classification was compared between the World Association of Sleep Medicine (WASM) 2006 and the WASM 2016 rules in 336 participants with apnea hypopnea index (AHI) ≥ 5; (2) determinants and features of rLM were investigated with logistic mixed regression in 172 participants with AHI ≥ 10 and respiratory disturbance index (RDI) ≥ 15, and (3) LM parameters were compared for patients with and without cardiovascular events and related to continuous positive airway pressure (CPAP) adherence.ResultsWASM-2016 scoring significantly reduced periodic limb movements of sleep (PLMS) frequency in OSA participants even when only considering the new periodicity criteria. Probability of rLM was strongly increased when respiratory events ended with an arousal, but rLM probability was lower for hypopneas and respiratory effort-related sleep arousal (RERAs) than for obstructive apneas. In participants with frequent non-respiratory PLMS, rLM were more frequent and behaved more PLMS-like. In participants without PLMS, rLM probability mostly depended on respiratory event features. LM parameters were neither related to cardiovascular event risk nor to CPAP-adherence.ConclusionsIt is likely that the PLMS frequency in OSA populations has been previously overestimated. Our results suggest that there are two types of rLM, true periodic ones that happen to synchronize with the respiratory events, and periodic appearing but respiratory driven LM, and that the presence of non-respiratory PLMS is instrumental in distinguishing between the two.     

Epworth Sleepiness Scale and sleep studies in patients with obstructive sleep apnea syndrome

Excessive daytime sleepiness (EDS) is the major symptom of patients with obstructive sleep apnea syndrome (OSAS). In this study, we examined the relationship between subjective EDS scored with the Epworth Sleepiness Scale (ESS), objective EDS measured with the multiple sleep latency test (MSLT) and sleep variables evaluated with polysomnography for patients with OSAS. Subjects were 10 patients (51.7+/-19.0 years old). The average ESS and MSLT scores were 10.6+/-5.6 and 7.7+/-5.6, respectively. There was no significant relationship between ESS and MSLT. The Multiple Sleep Latency Test had a significant negative relationship with the number of awakenings and the apnea/hypopnea index. No relationship was found between nocturnal hypoxia and either ESS or MSLT. Our findings suggest that objective EDS in OSAS is related with fragmentation of sleep, and that several patients are not aware of their EDS.     

Difference in the characteristics of subjective and objective sleepiness between narcolepsy and essential hypersomnia

The present study was conducted to investigate the difference in the characteristics of daytime sleepiness between narcolepsy and essential hypersomnia and to identify the relationship between the Epworth Sleepiness Scale (ESS) and the Multiple Sleep Latency Test (MSLT) in patients with these two disorders. Subjects consisted of 34 patients with essential hypersomnia (32.4 +/- 11.0 years old), 52 patients with narcolepsy (29.0 +/- 13.8 years old), and 45 control subjects (33.3 +/- 6.6 years old). The subjects completed the ESS and underwent MSLT following a regular sleep-wake schedule for over 2 weeks. The ESS scores were pathologically high and mean sleep latency on MSLT was short, not only in narcolepsy but also in essential hypersomnia. With respect to sleep latencies on each MSLT session, both essential hypersomnia and control subjects had the smallest value at 14:00, while narcolepsy lacked any statistical change at this time period. The correlation between ESS and mean sleep latency on MSLT was higher in essential hypersomnia than in narcolepsy, and the correlation was strongest for the session performed at 14:00. Based on the ESS and MSLT results, the severity of excessive daytime sleepiness was significantly milder in essential hypersomnia compared with that in narcolepsy. The results also indicate that diurnal variation of sleepiness was maintained, and the correlation between subjective and objective sleepiness was relatively maintained in essential hypersomnia compared to narcolepsy. It is suggested that the mild disease severity of essential hypersomnia contributed to the formation of these characteristics.     

Periodic leg movements in patients with Parkinson's disease are associated with reduced striatal dopamine transporter binding

We used single photon emission computed tomography (SPECT) to study striatal [¹²³I]β-CIT binding and polysomnography to study periodic leg movements during sleep (PLMS) in eleven patients with idiopathic Parkinson's disease (PD). The reduced striatal [¹²³I]β-CIT binding was significantly correlated with the number of PLMS. We propose that striatal dopaminergic nerve cell loss is involved in the increased number of PLMS in PD patients. Received: 26 April 2002, Received in revised form: 21 August 2002, Accepted: 29 August 2002 Correspondence to Svenja Happe, MD     

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.     

Evaluation of periodic limb movements in a putative animal model of restless leg syndrome

Restless leg syndrome (RLS) is a major healthcare burden with increasing prevalence. It has been demonstrated that periodic limb movements (PLM) can occur as an isolated phenomenon, but they are often associated with this syndrome and are the only symptom of this disorder that can be measured electrophysiologically. The aim of this study was to examine the sleep-wake behavior and the presence of limb movement in a rat model of RLS induced by lesioning the A11 dopaminergic nuclei with the neurotoxin 6-hydroxydopamine (6-OHDA). Rats were implanted with electrodes for electrocorticography and electromyography. Sleep recordings were monitored during light/dark periods lasting 12 hours each and were evaluated on days 7, 15, and 28 after injection of the drug or phosphate-buffered saline (PBS). A control group that did not receive any injection was also included. Wakefulness percentages were generated for 4-hour segments of the dark period, yielding the following 3 bins: 7 PM to 11 PM, 11 PM to 3 AM, and 3 PM to 7 PM. Additionally, slow wave sleep, paradoxical sleep, wakefulness, and limb movements were evaluated over the entire 12 hours of the light/dark cycle. All A11-lesioned rats exhibited an increased percentage of wakefulness during the last block of the dark period, as would be expected for an animal model of this syndrome. In addition, at all time points after lesioning, these animals presented increased frequencies of limb movement during both the light and the dark periods. These alterations were reversed by the acute administration of the dopaminergic agonist pramipexole. This animal model strengthens the notion that 6-OHDA-induced A11 lesions can be a valid animal model for RLS and PLM.