Search

Restless legs syndrome (RLS) is a neurological disorder that causes insomnia and daytime functional disability due to an urge to move the legs usually accompanied by uncomfortable sensations. Non-pharmacologic treatment includes regular sleep habits and exercise. Iron supplementation is indicated for patients with low serum ferritin levels. Antidepressants, antihistaminergics, and dopamine antagonists should be reduced or discontinued because they induce RLS symptoms. Dopamine agonists and alpha 2-delta ligands are the first-line pharmacological treatments for RLS.

Movement and behavior disorders developing during sleep or in the transitional state from sleep to wakefulness are mostly unfamiliar to Japanese neurologists, primarily because these disorders are objects of basic research. In addition, the patients with sleep related movement and behavior disorders (SRMBD) show no signs and symptoms in our consulting rooms, and cannot be identified without polysomnography (PSG) attended by trained sleep technologists. Although attended PSG is not widely available in Japan, some kinds of SRMBD ought to be clinical targets for neurologists, and they are the scope of this review.

Sleep related movement disorders (SRMD) are characterized by simple, stereotyped movements occur during sleep, with the exception of restless legs syndrome (RLS). RLS has the following essential features; an urge to move the legs usually accompanied by uncomfortable sensation in the legs, improvement of symptoms after movement (non-stereotypical movements, such as walking and stretching, to reduce symptoms), and symptoms occur or worsen during periods of rest and in the evening and night. However, RLS is closely associated with periodic limb movement, which shows typical stererotyped limb movements. In the International Classification of Sleep Disorders, 3rd edition, sleep disturbances or daytime symptoms are prerequiste for a diagnosis of SRMD. We here review diagnosis and treatment of SRMD.

Many patients with Parkinson's disease (PD) complain about sleep disturbances. These symptoms originate from motor symptoms, nocturnal problems, psychiatric symptoms, and other sleep disorders including Excessive daytime sleepiness (EDS), REM sleep behavior disorder (RBD), Restless legs syndrome (RLS), and Sleep apnea syndrome (SAS). Especially, RBD is paid attention to prodromal symptoms of PD. Also, one third of patients with PD have RBD symptoms. Moreover, RBD is one of aggravating factors of motor symptoms, autonomic dysfunctions, and dementia. Now, the evidence based medicine for sleep disturbances is lack in patients with PD. We need to evaluate various causes of sleep disturbances in detail and deal with individuals.

The symptoms of restless legs syndrome (RLS) can be managed effectively by treatment. The pathophysiology of primary RLS is only partly understood; however, a strong association with brain iron deficiency, which possibly impairs dopaminergic function, has been identified. Dopamine agonists are the mainstay of RLS treatment, but other therapies, including gabapentin, benzodiazepines, and low-potency opioids, are also commonly employed. Recent evidence-based guidelines recommend dopamine agonists or alpha-2-delta ligands as the first-line treatment for RLS depending on patients' clinical background, comorbidity, and severity of the symptoms. In this review, we focus on the pathophysiology, comorbidity, differential diagnosis, and novel treatment approaches of RLS.

Restless legs syndrome (RLS) is a clinically important, common disease and should be diagnosed and treated early and adequately. At present, there have been no clinical biomarkers or methodologies that can contribute to the correct diagnosis of RLS, RLS should be diagnosed on the basis of 4 essential criteria: urge to move the legs, improvement after movement, and worsening or occurrence of symptoms in the evening and at rest. When applying the criteria, RLS mimics should be ruled out and comorbid diseases should be taken into account. The origin and pathogenesis of RLS are still under investigation; however, iron deficiency in the brain has been observed on imaging and cerebrospinal fluid analyses of patients with RLS. In contrast, the results of neuroimaging studies evaluating brain dopaminergic functions in patients with RLS have yielded inconclusive results, although involvement of the hypothalamus (A11) is thought to cause impaired dopaminergic modulation in the dorsal horn and intermediolateral nucleus, resulting in the restlessness of legs.

Background: Little is known about the diagnosis and management of restless legs syndrome (RLS) in Japanese neurology clinics., Objective: To validate the diagnostic criteria of the International RLS Study Group (IRLSSG) and the treatment algorithm of the Mayo Clinic in a Japanese neurology clinic setting and to clarify the features of Japanese patients with idiopathic RLS., Methods: Patients with RLS symptoms were examined by a neurologist and the assessment included neurological examination, tests for periodic limb movements (PLM) and dopaminergic response, and the clinical diagnosis was made according to IRLSSG diagnostic criteria. Patients diagnosed with idiopathic RLS were treated with dopaminergic agents and the efficacy was evaluated., Results: The study subjects were 151 Japanese patients who presented with RLS symptoms. Idiopathic RLS was diagnosed in 113 patients, secondary RLS in 16 and RLS mimics in 22. The cause of RLS mimics was either myelopathy, radiculopathy or neuropathy in 11 patients. The mean age of patients with idiopathic RLS was 50.1 (SD 20.0) years, 63% were woman, 97% had daily RLS, 31% had family history (40% of the early-onset subgroup), 86% reported unpleasant sensations in the lower legs, 43% had PLM in the daytime suggested immobilization test, 81% suffered from insomnia, 49% had limitations of work and activities, 71% reported impaired mood, 27% had consulted physicians about their symptoms, 4% had been diagnosed with RLS, 73% improved after dopaminergic treatments, and 33% experienced complete remission., Conclusions: The clinical features of Japanese patients with idiopathic RLS were identical to those reported in western countries, which suggests that IRLSSG diagnostic criteria and Mayo Clinic treatment algorism are valid in Japanese neurology clinics. Both patients and physicians were not fully aware of RLS in this country. Neurological examination was important in excluding RLS mimics and making a diagnosis of RLS.

Restless legs syndrome (RLS) is known to occur secondary to various medical conditions such as iron deficiency, pregnancy, end-stage renal disease, and neuropathy. Secondary RLS usually occurs later in the life and in the absence of a family history of RLS. Diagnosis of secondary RLS may be difficult, particularly in patients with neurological comorbidities. Sensory disturbance due to neurological disorder may mimic the symptoms of RLS symptom. In distinguishing between RLS and RLS mimics, neurophysiological findings, in addition to a detailed neurological examination, are helpful. Treatment of secondary RLS often requires management of the background medical condition. Iron supplementation is useful in patients with iron deficiency. Dopamine agonists are usually effective for both primary and secondary RLS; however, an increased dose of dopamine agonist may be necessary in some secondary RLS cases, particularly in uremic RLS. In patients with end-stage renal disease on hemodialysis, management of daytime symptoms, particularly during the hemodialysis sessions, may be necessary. Secondary RLS is still an unrecognized and underdiagnosed disorder. Medical practitioners should be aware of comorbid RLS in patients with neurological conditions that could be the cause of RLS.

Restless legs syndrome (RLS) is a sensorimotor disorder, characterized by an irresistible urge to move the legs and usually accompanied or caused by uncomfortable and unpleasant sensations. It begins or worsens during periods of rest or inactivity, is partially or totally relieved by movement and is exacerbated or occurs mainly in the evening or night. People suffering from RLS are estimated to represent 2-3% of the general Japanese population, which is relatively lower than the estimated prevalence in western countries. Supportive diagnostic critevia include family history, the presence of periodic-leg movements (PLM) when awake or asleep, and a positive response to dopaminergic treatment. RLS phenotypes include an early onset form that is usually idiopathic with frequent familial history and a late onset form that is usually secondary to other somatic conditions that are causative factors in RLS occurrence. In all patients presenting with complaints of insomnia or discomfort in the lower limbs, diagnosis of RLS should be considered. RLS should be differentiated from akathisia, which is an urge to move the whole body in the absence of uncomfortable sensations. Polysomnographic studies and the suggested immobilization test (SIT) can detect PLM in patients that are asleep or awake. RLS may cause severe sleep disturbances, poor quality of life, depressive and anxious symptoms, and may be a risk factor for cardiovascular disease. Secondary RLS may occur due to iron deficiency, end-stage renal disease, pregnancy, peripheral neuropathy and drug use including antipsychotics and antidepressants. Small fiber neuropathy can trigger RLS or mimic its symptoms. RLS is associated with many neurological disorders, including Parkinson disease and multiple system atrophy; althoughit does not predispose to these diseases. A symptom rating scale for RLS authorized by the International RLS Study Group (IRLS) would facilitate accurate diagnosis of this condition.

Restless legs syndrome (RLS) is a sensorimotor disorder that is frequently associated with periodic leg movements (PLMS). RLS is generally considered to be a central nervous system (CNS)-related disorder although no specific lesion has been found to be associated with the syndrome. Reduced intracortical inhibition has been demonstrated in RLS by transcranial magnetic stimulation. Some MRI studies have revealed the presence of morphologic changes in the somatosensory cortex, motor cortex and thalamic gray matter. The results of SPECT and PET studies showed that the limbic and opioid systems also play important roles in the pathophysiology of RLS. A functional MRI study revealed abnormal bilateral cerebellar and thalamic activation during the manifestation of sensory symptoms, with additional red nucleus and reticular formation activity during PLMS. PLMS is likely to occur in patients with spinal cord lesions, and some patients with sensory polyneuropathy may exhibit RLS symptoms. RLS symptoms seem to depend on abnormal spinal sensorimotor integration at the spinal cord level and abnormal central somatosensory processing. PLMS appears to depend on increased excitability of the spinal cord and a decreased supraspinal inhibitory mechanism from the All diencephalic dopaminergic system. RLS symptoms respond very dramatically to dopaminergic therapy. The results of analysis by PET and SPECT studies of striatal D2 receptor binding in humans are inconclusive. However, studies in animal models suggest that the participation of the All dopaminergic system and the D3 receptor in RLS symptoms. The symptoms of RLS are aggravated in those with iron deficiency, and iron treatment ameliorates the symptoms in some patients. Neuroimaging studies, analysis of the cerebrospinal fluid, and studies on postmortem tissue and use of animal models have indicated that low brain iron concentrations and dysfunction of iron metabolism and intracellular iron may play key roles in the pathogenesis of RLS. The "iron-dopamine model" explains that iron deficiency in the brain causes an abnormality in the dopaminergic system leading to manifestation of RLS. Genetic factors are also important in the development of RLS. A positive family history for RLS has been reported by 40% to 60% of RLS patients. Five loci (RLS 1: 12q, RLS 2: 14q, RLS 3: 9p, RLS 4: 2q, RLS 5: 20p) have been described. Genome-wide association studies have identified variants within the intronic or intergenetic regions of MEIS1 (2p), LBXCOR1/MAP2K5 (15q), BTBD9 (6p), neuronal nitric oxide synthase (NOS1) (12q) and protein tyrosine phosphatase receptor type delta (9p) genes. In conclusion, disturbances in the central dopaminergic system, disturbances in iron metabolism, and genetics seem to be the primary factors in the pathophysiology of RLS.

Restless legs syndrome (RLS) has gradually been recognized as a cause for insomnia in adults, but there have been few reports about children with RLS in Japan. Here we described seven pediatric RLS patients. All of the parents of our patients had difficult times to make their children sleep due to irritability, restlessness, and demanding bedtime routines. All patients had asked their parents to rub their feet in bed, and it took more than half an hour to soothe them until they fell asleep. Their mothers had been exhausted from this night-time routine. However, they did not consider the routine abnormal, as it had been their habitual behavior since infancy. Some parents were too distressed or embarrassed to describe the symptoms of their child properly. Five patients had clear family history and none had obvious periodic leg movements during sleep. All patients showed low levels of ferritin and iron supplementation was effective in five cases. In the severest two cases, pramipexole, but not iron, was dramatically effective. Both patients started to show RLS symptoms in the early days of infancy, which may suggest more severe hereditary dopaminergic dysfunction. RLS does occur in childhood and pediatricians should bear it in mind as one of the differential diagnoses when seeing children who are irritated and/or having difficulty in initiating their sleep.

The periodic limb movements (PLM) are defined as stereotyped, periodic movements of the legs and/or upper limbs during sleep. The patient exhibits dorsifilexion of the ankle and extension of the big toe with occasional flexion of the knee and hip. PLM originally was described as "nocturnal myoclonus" by Symonds in 1953. Recently, the term "nocturnal myoclonus" has been replaced with PLM, because the movements are slower than true myoclonic movement. The appearance of PLM was reported in sleep apnea syndrome, delayed sleep phase syndrome, narcolepsy, spinal cord tumor, diabetes mellitus and uremia. The prevalence of PLM statistically increase with age. Patients with PLM show excessive daytime sleepiness or insomnia. Several reports show the difficulty recognizing periodic limb movement disorder (PLMD) without polysomnography (PSG). The diagnosis of PLMD is established only by PSG.