Pharmacological Management of Restless Legs Syndrome and Periodic Limb Movement Disorder in Children.

Restless legs syndrome (RLS) and periodic limb movement disorder (PLMD) are under-recognized sleep disorders in children and adolescents. Several recent epidemiological studies have shown that RLS and PLMD are common in the pediatric population, and if left untreated, may lead to cardiovascular and neurocognitive consequences. Therefore, early diagnosis and intervention may help preventing long-term consequences. The management of RLS and PLMD in children involves both non-pharmacologic and pharmacologic approaches. Although there is emerging literature supporting medical therapy in children with RLS and PLMD, the overall experiences with these medications remain limited. Most children and adolescents with RLS and PLMD have low iron storage; therefore, iron therapy should be considered as the first line of treatment in children. Currently, there is no FDA-approved medication for RLS and PLMD in children. There is increasing evidence on the effectiveness of dopaminergic medications in children but the data are quite limited. Other medications such as α2δ-1 ligands, benzodiazepine, and clonidine are frequently used, but have not been adequately investigated in children. Further studies are needed to evaluate the safety and efficacy of pharmacologic therapy for RLS and PLMD in children.

Periodic Limb Movements and White Matter Hyperintensities in First-Ever Minor Stroke or High-Risk Transient Ischemic Attack.

Study Objectives: Emerging evidence suggests that periodic limb movements (PLMs) may contribute to the development of cerebrovascular disease. White matter hyperintensities (WMHs), a widely accepted biomarker for cerebral small vessel disease, are associated with incident stroke and death. We evaluated the association between increased PLM indices and WMH burden in patients presenting with stroke or transient ischemic attack (TIA), while controlling for vascular risk factors and stroke severity. Methods: Thirty patients presenting within 2 weeks of a first-ever minor stroke or high-risk TIA were prospectively recruited. PLM severity was measured with polysomnography. WMH burden was quantified using the Age Related White Matter Changes (ARWMC) scale based on neuroimaging. Partial Spearman's rank-order correlations and multiple linear regression models tested the association between WMH burden and PLM severity. Results: Greater WMH burden was correlated with elevated PLM index and stroke volume. Partial Spearman's rank-order correlations demonstrated that the relationship between WMH burden and PLM index persisted despite controlling for vascular risk factors. Multivariate linear regression models revealed that PLM index was a significant predictor of an elevated ARWMC score while controlling for age, stroke volume, stroke severity, hypertension, and apnea-hypopnea index. Conclusion: The quantity of PLMs was associated with WMH burden in patients with first-ever minor stroke or TIA. PLMs may be a risk factor for or marker of WMH burden, even after considering vascular risk factors and stroke severity. These results invite further investigation of PLMs as a potentially useful target to reduce WMH and stroke burden.

The additive impact of periodic limb movements during sleep on inflammation in patients with obstructive sleep apnea.

RATIONALE: Both periodic limb movements during sleep (PLMS) and obstructive sleep apnea (OSA) are major causes of sleep disorders and have been associated with systemic inflammation and cardiovascular events. However, it is uncertain whether in combination they promote a higher inflammatory response and greater risk of cardiovascular events than each condition alone. OBJECTIVES: To investigate whether the presence of PLMS is associated with increased inflammation in patients suspected of having OSA. METHODS: In 342 patients who underwent polysomnography to diagnose OSA, plasma C-reactive protein (CRP) and fibrinogen levels were measured. MEASUREMENTS AND MAIN RESULTS: OSA was found in 254 patients, with 46 also having PLMS. Among the 88 patients who did not have OSA, 8 had PLMS. Plasma CRP and fibrinogen levels in the group with both PLMS and OSA were higher than in patients with neither OSA nor PLMS and in patients with OSA only (CRP: 0.20 ± 0.48 vs. 0.09 ± 0.15 vs. 0.13 ± 0.18 mg/dl, P = 0.03; fibrinogen: 298.2 ± 76.1 vs. 269.0 ± 57.1 vs. 270.0 ± 52.6 mg/dl, P < 0.01). Multivariate analysis showed that the presence of PLMS was associated with higher plasma CRP levels (ß = 0.1401, P < 0.01) and fibrinogen levels (ß = 0.1359, P = 0.01) independently from other clinical variables such as body mass index and the severity of OSA. CONCLUSIONS: PLMS were positively associated with plasma CRP and fibrinogen levels in patients suspected of having OSA. Because plasma levels of these proteins have been established as predictive factors of future cardiovascular events, the presence of PLMS may be a useful clinical sign to identify patients with OSA at high risk of cardiovascular events.

Characterization of periodic upper limb movement disorder in a patient with restless arms syndrome.

BACKGROUND: Restless legs syndrome (RLS) and the frequently associated periodic limb movements (PLM) are common neurological disorders whose pathophysiology remains elusive. We report on the case of a 40-year-old patient presenting with severe restlessness in the upper limbs, a poorly known variant of RLS. CASE REPORT: Video-polysomnography was performed because of the associated poor sleep quality and daytime sleepiness evocative of PLM. An electromyogram of the extensor carpi radialis muscle was added. Remarkably, our patient had movements of repeated extension of the small finger that contrasted with the extension of the hallux, characteristic for PLM. Pramipexol was an effective treatment relieving the patient's upper limbs of discomfort and ameliorating her restless sleep. CONCLUSIONS: Involvement of the upper limbs in RLS is relatively common, but restlessness may be located on the upper limbs solely. One should be aware of the upper limb variant, and that treatment by dopaminergic agonists proves to be very efficient.

Diffuse subcortical band heterotopia, periodic limb movements during sleep and a novel "de novo" mutation in the DCX gene.

Mutations of the DCX gene (Xp22.3) cause X-linked lissencephaly in males and double cortex syndrome (DCS) or subcortical band heterotopia (SBH) in females. SBH is characterized by bilateral bands of grey matter interposed in the white matter between the cortex and the lateral ventricles. The main clinical manifestation in patients with SBH is epilepsy, which may be partial or generalized and is intractable in approximately 65% of the patients. An association of periodic limb movements (PLMs) and SBH has not been documented previously. We describe a 2-year-old girl affected by SBH with epilepsy and periodic limb movements (PLMs), in whom a novel "de novo" missense substitution, Met1Val (M1V), was identified in the DCX gene. Physiopathological links between PLMs and SBH are discussed.

Restless legs syndrome and periodic limb movements.

The history, clinical aspects, and treatment of restless legs syndrome (RLS), a heterogeneous distressing sensorimotor disorder, and periodic limb movements (PLMs) that are the typical motor accompaniment of the syndrome, are described. A positive family history, a positive response to dopaminergic treatment, and the presence of PLM while awake or asleep are supportive criteria for the diagnosis of the disorder. RLS and PLM occur more frequently at the beginning of night and exponentially decline across sleep cycles, suggesting circadian influences. Altered circadian rhythmicity in dopamine metabolism and enhanced circadian variations in dopaminergic functions have been reported in the disorder. Dysfunction or atrophy of A11 cells from the diencephalic-spinal dopamine A11 system has been suggested to explain the efficacy of dopaminergic drugs in relieving RLS symptoms and the circadian rhythmicity of RLS. Studies support the hypothesis that the A11 dopaminergic neurons and spinal pathways may be more involved in the pathophysiology of RLS than the nigrostriatal system. Neurophysiological evidence indicates that the involuntary movements in RLS may be of spinal or propriospinal origin. Despite these findings, however, the pathogenic mechanisms underlying the peculiar sensory and motor manifestations of RLS remain unexplained. Among the current treatment options offered for the treatment of RLS, dopaminergic agents have provided the best evidence for efficacy in symptom relief.

Daytime sleepiness in patients with CRF: impact of nocturnal hemodialysis.

BACKGROUND: Patients with end-stage renal disease (ESRD) have a high prevalence of sleep disorders, which are not improved by conventional hemodialysis (CHD). Although sleep disorders are commonly associated with complaints of excessive daytime sleepiness, the severity and pathogenesis of daytime sleepiness has not been evaluated objectively in patients with ESRD. Nocturnal hemodialysis (NHD) is a new technique that provides better clearance of uremic toxins than CHD and, consequently, may improve sleep quality and daytime sleepiness. The authors wished to determine the severity and pathogenesis of daytime sleepiness in patients with ESRD and evaluate the impact of NHD. METHODS: Sleep quality was monitored by overnight polysomnography, and daytime sleepiness was assessed by the multiple sleep latency test (MSLT). These measurements were performed in 24 patients (15 men and 9 women, 44 +/- 10 years) while on treatment with CHD and were repeated in 15 patients after conversion to NHD. RESULTS: The majority (54%) of patients on CHD were pathologically sleepy (somnolent group, mean sleep latency <5 minutes), and, in comparison with the remaining patients (alert group, mean sleep latency >5 minutes), their blood urea nitrogen (BUN; 77.9 +/- 9.8 v 60.2 +/- 12.0 mg/dL, P < 0.001; 27.8 +/- 3.5 v 21.5 +/- 4.3 mmol/L; P < 0.001), and periodic limb movement (PLM) index (57 +/- 47 v 6 +/- 10/hr; P = 0.002) were significantly higher. Furthermore, sleep latency was correlated with BUN (R = 0.58, P = 0.008). After conversion to NHD, there was a significant fall in BUN and the severity of sleep apnea, but the overall frequency of PLM and sleep fragmentation remained elevated. Nevertheless, there was a trend for the Somnolent group to become less sleepy on NHD, and this was associated with a modest reduction in the frequency of PLM. CONCLUSION: Excessive daytime sleepiness occurs in approximately 50% of patients with ESRD. The etiology appears to be related both to uremia and sleep fragmentation associated with PLM.

Subjective sleep quality and suggested immobilization test in restless leg syndrome and periodic limb movement disorder.

The severity of restless leg syndrome (RLS) and/or periodic limb movement disorder (PLMD) was investigated by using a suggested immobilization test (SIT) and by measuring the influence of these disorders on the subjective sleep quality as assessed by the Pittsburgh Sleep Quality Index (PSQI). Patients with RLS and those with both RLS and PLMD showed remarkably high values for PSQI and SIT, whereas patients with PLMD only showed normal values for PSQI. These findings suggest that there is only a small pathological significance for periodic limb movements, and demonstrate the efficacy of SIT and PSQI for evaluating the severity of these disorders.