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PubMed2004

Gabapentin versus levodopa for the treatment of Restless Legs Syndrome in hemodialysis patients: an open-label study.

BACKGROUND: Restless Legs Syndrome (RLS), a common problem increasing morbidity and mortality in hemodialysis (HD) patients, affects 20-30% of uremic patients. Our aim was to find the efficacy of gabapentin in the treatment of RLS in HD patients by comparing a largely used drug, levodopa. METHODS: Patients with RLS answered three questionnaires (RLS rating scale proposed by IRLSSG, the Short Form (SF)-36 and the Pittsburgh Sleep Quality Index) for the evaluation of severity of RLS, effects on quality of life and quality of sleep. RESULTS: Fifteen patients (4.7%) (5 F, 10 M) with a mean age of 45.8+/-15.3 years got RLS diagnosis. When we compare the two drugs for severity of RLS symptoms relief, the effect of gabapentin was more significant (p<0.001). Gabapentin significantly improved general health, body pain and social functions (p<0.001). Moreover, regarding sleep parameters, gabapentin was significantly superior to levodopa for sleep quality, sleep latency (p<0.001) and sleep disturbance (p<0.000). CONCLUSION: To our knowledge this was the first study comparing gabapentin and levodopa efficacy for the treatment of RLS in HD patients. Our results suggested that gabapentin is an effective drug for the management of RLS in hemodialysis patients.

Adult↗
PubMed2006

Use of pramipexole in REM sleep behavior disorder: results from a case series.

BACKGROUND AND PURPOSE: Rapid eye movement (REM) sleep behavior disorder (RBD) has a known association with other medical conditions, including narcolepsy and neurodegenerative diseases such as synuclienopathies. RBD is currently treated with clonazepam as a first-line therapy. Recent research suggests that the pathophysiology underlying RBD may involve a dopaminergic deficiency, given its association with Parkinson syndromes and restless legs syndrome (RLS). We report on the efficacy of pramipexole, a dopaminergic D2-3 receptor agonist, in the treatment of RBD. PATIENTS AND METHODS: The first 10 consecutive patients presenting with a history and polysomnographically confirmed RBD were given pramipexole as either a single dose before bedtime or as a divided dose regimen with the first dose given in the early evening and the second dose at bedtime. Medication was titrated to control RBD symptoms and the clinical response was monitored through interviews with the patient, spouse, and close family members during the course of the study at regularly scheduled follow-up visits. RESULTS: The mean length of treatment was 13.1 months, and the average total evening dose of pramipexole at the end of the study was 0.89+/-0.31 mg. A divided dose regimen of pramipexole was used in 56% of patients remaining on pramipexole. We found that 89% of patients experienced either a moderate reduction or complete resolution in the frequency of RBD symptoms throughout the duration of the study. Moreover, 67% reported at least a moderate reduction in the severity of remaining symptoms. CONCLUSIONS: Pramipexole markedly reduced the frequency and severity of RBD symptoms and appeared to maintain efficacy for up to 25 months as assessed at follow-up visits. Clonazepam may have numerous unwanted side effects in the elderly or narcoleptics with RBD, such as prominent sedation and the potential exacerbation of underlying obstructive breathing in sleep. The potential role of pramipexole in improving RBD and its associated dopamine deficient syndromes warrants further research in the use of dopaminergic agonists as a potential first-line alternative therapy for RBD.

Aged↗
PubMed2006

CAG repeats in Restless Legs syndrome.

Recent reports established an association of restless legs syndrome (RLS) and spinocerebellar ataxia (SCA) type 1, 2, and 3. To evaluate the contribution of SCA alleles to idiopathic RLS we investigated the CAG repeat length at the SCA1, SCA2, SCA3, SCA6, SCA7, and SCA17 loci in 215 patients who fulfilled the clinical criteria of RLS and presented periodic leg movements in sleep (PLMS) in polysomnographic recording. Fifty percent of patients had a positive family history of RLS. We found one intermediate (CAG)(43) allele for SCA17 in a 44-year-old female with RLS starting at the age of 43. Neurologic examination and family history were unremarkable in this patient. Otherwise, allele distribution did not differ between RLS patients and healthy controls. Stratification for age, age of onset, sex, peripheral neuropathy, and sporadic or familial RLS revealed no effect. Thus, CAG repeat length in the investigated genes is not a major determinant of idiopathic or familial RLS.

Adult↗
PubMed1994

Nocturnal eating syndrome in adults.

Ten adult subjects were referred to our sleep disorders center complaining of difficulty in maintaining sleep due to frequent and recurrent awakenings to eat or drink. All patients manifested more than one episode per night, characterized by compulsive food seeking and a return to sleep only after adequate food intake. Food-seeking drive was described as an urgent abnormal need to swallow food and was associated with an absence of real hunger. Six subjects showed an elective nighttime intake of carbohydrates, and in all cases only edible substances were injected. The patients were always fully awake during the episodes and could clearly recall them in the morning. Polysomnographic investigation showed low levels of sleep efficiency, a high number of awakenings and a strict relation between nocturnal eating episodes and nonrapid eye movement (NREM) sleep. The average length of each episode was 3.5 minutes. The "eating latency", that is the interval between awakening and chewing start, was shorter than 30 seconds in 50% of the episodes. No medical, hormonal or neurological disorders were found during clinical and laboratory investigations. Body mass index was abnormally high in six patients. Anorexia nervosa and bulimia were carefully excluded. Various psychiatric disturbances were found in nine subjects, who were nevertheless well-functioning adults. Concurrent dyssomniac disorders, such as narcolepsy or periodic leg movements occasionally associated with restless legs syndrome, were diagnosed in five patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2004

Functional neuroimaging studies in restless legs syndrome.

Functional neuroimaging studies may contribute to elucidate pathophysiological mechanisms of the restless legs syndrome (RLS) which still remain unclear. Studies in patients with RLS have been performed using functional magnetic resonance imaging (fMRI), single photon emission computed tomography (SPECT) and, more recently, positron emission tomography (PET). SPECT and PET studies revealed some controversial results of the pre- and postsynaptic dopaminergic neurotransmission system and cerebral metabolism in RLS probably reflecting a dysfunction of the central dopaminergic system. However, it still has to be determined whether these alterations affect the nigrostriatal and/or other central dopaminergic systems like the diencephalospinal or mesolimbic pathway and whether they are the primary mechanisms or only secondary phenomena within the manifestation of RLS symptoms. A subtle receptor dysfunction or a synaptic dopaminergic deficit may play a major role. fMRI investigations of RLS patients revealed an activation in the red nuclei and brainstem close to the reticular formation during the symptomatic period, suggesting that subcortical cerebral generators are involved in the pathogenesis of RLS. However, both techniques are not yet clinically relevant methods to differentiate RLS from other movement disorders during sleep. Further investigations, especially at night when RLS symptoms are most pronounced, will lead to a better understanding of the mechanisms underlying RLS.

Brain↗
PubMed1996

A questionnaire study of 138 patients with restless legs syndrome: the 'Night-Walkers' survey.

After verifying the diagnosis of restless legs syndrome (RLS) in 105 patients who are part of a nationwide support group, we undertook a telephone survey of their symptomatology. We then compared the answers with those of 33 of our own RLS patients who had undergone a neurologic examination and had a periodic limb movement in sleep (PLMS) index of > 5 (number per hours of sleep). Although RLS has generally been considered to be a condition of middle to older age, the results for the support group, and for our patients, are similar in that more than a third of the patients in each group experienced their first symptoms before the age of 10. Initial lack of diagnosis or misdiagnosis by a physician were common and the symptoms were commonly thought to be psychogenic whatever the age of onset. In some cases, young age-onset RLS was severe from the start. For younger age-onset patients whose symptoms were severe enough to seek immediate medical attention, confounding or misdiagnosis included "growing pains" and attention deficit hyperactivity disorder. However, medical attention was generally not sought until the fourth decade. Most respondents stated that this was because their symptoms were mild at onset and then progressed. In the older age-onset patients, misdiagnoses also included skin irritation, arthritis, and malingering. A total remission of symptoms of a month or more was present in at least 15% of the individuals in all groups surveyed. More than 50% of the respondents know of one or more first-degree relatives affected by RLS. Five of our 33 patients had RLS initially triggered either by diabetic peripheral neuropathy or lumbosacral radiculopathy.

Adult↗
PubMed1988

Animal models of chronic anxiety and "fearlessness".

Three behavioral animal models have been described: a feline and a rodent model of chronic anxiety, and a rodent model of "fearless" behavior. The models have been obtained by pre- or perinatal exposure to diazepam (DZ) or RO 15-1788 which produced enduring postnatal deficits or enrichment, respectively, of brain benzodiazepine (BDZ) receptors. The receptor-deficient one-year-old cat progenies showed hyperarousal, unabated restless behavior, delayed acquisition of instrumentally conditioned behavior, bizarre escape responses and absence or reduced alpha-like EEG activity. The receptor-deficient rat progencies, studied at the age of 5-6 months, showed a reduction of time spent in deep slow wave sleep, and inability to habituate to novel environment, such as the radial arm maze. In the maze, the behavior of these progenies was characterized by delayed and incomplete exploratory activity often terminated by sudden escape, numerous fecal deposits and significantly more frequent than normal errors of "working memory." On the other hand, in all aspects, the receptor-enriched progenies were superior to the control animals as well as to the receptor-deficient group, particularly when the animals were challenged by novel and "intimidating" visual and/or auditory stimuli. In addition, 12 out of 51 receptor-deficient rats reared for 18 months developed mammary fibroadenomas, while no such tumors were found in the group of 44 vehicle-exposed control animals. Increased density and affinity of BDZ brain receptors was also observed after adult rats were treated with RO 15-1788 administered water for 7 or 14 days.

Animals↗
PubMed1989

Movement disorder of premature infants with severe bronchopulmonary dysplasia: a new syndrome.

A previously unrecognized, striking movement disorder has been observed in 10 premature infants with severe bronchopulmonary dysplasia. Chronic hypoxemia, hypercarbia, bronchospasm, and inadequate nutrition were present in all. The movement disorder developed from approximately the third postnatal month. The dominant movements involve the limbs, neck, trunk, and oral-buccal-lingual structures. The limb movements were most prominent distally and consisted of rapid, random, jerky movements (similar to chorea) and "restless" movements (similar to akathisia). Similar movements of the neck and face were observed; tongue movements had a "darting" quality. The oral-buccal-lingual movements were similar to the dyskinesia of older patients. Movements were exacerbated during episodes of respiratory failure and attenuated during sleep. All infants exhibited feeding disorders, largely due to tongue movements. In 3 infants treated with clonazepam, there was striking improvement in motor function, including feeding. The natural history was partial or complete resolution or a static course. Thus, of the 7 surviving infants, the movements were absent (without therapy) at 15, 18, and 30 months of age. In the remaining 4 infants (3 of whom receive clonazepam), the movements, though attenuated, persisted at 6, 12, 15 and 21 months of age, respectively. Neuropathologically, 1 infant showed neuronal loss with astrocytosis in caudate, putamen, globus pallidus, and thalamus. These data defined a previously unrecognized extrapyramidal movement disorder of infants with severe bronchopulmonary dysplasia; pathogenesis may be related to chronic hypoxemia.

Bronchopulmonary Dysplasia↗
PubMed2002

Erectile dysfunction and symptoms of sleep disorders.

STUDY OBJECTIVES: Sleep apnea often is associated with impotence and/or erectile dysfunction (ED). The purpose of this study was to test whether a presentation for ED confers a pretest probability for obstructive sleep apnea hypopnea syndrome (OSAHS). DESIGN: A self-report survey for sleep complaints was conducted in consecutive male patients (>16 years of age) presenting to a urologic practice site. SETTING: The survey was provided to new and follow-up out-patients over a 2 month period of time. Other information collected included the presenting complaint, the clinical diagnosis for ED, and history of preexisting medical conditions. PARTICIPANTS: N/A. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: 285 males [91% of the sample: 50 years old (range 16-82) and body mass index, 27.3 (range 16.8-52.5)] completed the survey. 181 (63%) had complaints of ED; of those, 76% had a final diagnosis of organic and 8.2%, psychogenic or both psychogenic and organic ED. Of all respondents, 35.4% reported persistent snoring, 14% reported persistent waketime sleepiness or fatigue, and 26.8% were at "high risk" (Netzer et al., 1999) for OSAHS. Some were high risk for insomnia (13.6%) and restless legs syndrome or for narcolepsy (2% each). There was a correlation between those with ED complaints (p<0.014) or those with a final diagnosis of organic ED (p<0.029) and snoring. In a logistic model that included age, snoring, and preexisting conditions, only age, depression, and history of hypercholesterolemia, were found to vary significantly among those with and without ED. CONCLUSIONS: Urology patients will report a variety of sleep problems, but neither persistent snoring nor suspected OSAHS is correlated uniquely to ED.

Adolescent↗
PubMed2006

RLS patients: who are they?

Four essential diagnostic criteria for restless legs syndrome (RLS) have been identified. Patients experience an urge to move the legs, which typically begins or worsens during periods of rest. The symptoms are at least partially relieved by movement, and are typically worse in the evening and night than in the day. All four criteria are necessary to confirm the diagnosis of RLS. In addition, a family history of RLS, the presence of periodic leg movements in sleep, and a positive response to dopaminergic therapy are useful supportive clinical features to confirm the diagnosis. Whilst many cases of RLS are idiopathic, secondary RLS is often observed in pregnant women, patients who have severe renal dysfunction, or in those with iron deficiency. Several other conditions have symptoms similar to those of RLS, but a detailed patient history is usually sufficient to identify these differential diagnoses. The accurate diagnosis and appropriate treatment of RLS should result in considerable improvements in patients' quality of life.

Diagnosis, Differential↗
PubMed1983

Etomidate infusion. Its use in anaesthesia for general surgery.

Etomidate has been studied in two groups of patients. In Group 1, 50 patients received etomidate 100 micrograms/kg/minute with fentanyl and a muscle relaxant, ventilation being with air and oxygen (50%). The technique gave a smooth, pleasant induction with all patients asleep within 2 minutes. The incidence of pain on infusion was 6% and of myoclonus 6%. Cardiovascular changes were minimal, the most common finding being persistent tachycardia. The mean recovery time was 9.1 minutes. There was no incidence of awareness, recall, or thrombophlebitis, but a 20% incidence of nausea and vomiting. In Group 2, 20 patients received the same dosage of etomidate to supplement spinal anaesthesia for lower abdominal surgery. The technique worked most satisfactorily, with patients falling quietly to sleep within 2-3 minutes with no hiccoughs, coughing or laryngospasm. Six patients exhibited myoclonus, one being severe. In no case did myoclonus interfere with the operation. The cardiovascular system remained stable in all patients. Mean recovery time was 16.1 minutes (range 3-38 minutes). Twitching and restlessness were the main complications during recovery.

Aged↗
PubMed1998

Treatment of restless leg syndrome with pergolide--an open clinical trial.

Dopaminergic treatment with levodopa (L-dopa) has been proven as the treatment of first choice in patients with restless leg syndrome (RLS). Augmentation of symptoms and end-of-dose rebound phenomena under L-dopa/decarboxylase inhibitor treatment present major problems in some patients. To evaluate the efficacy of pergolide in RLS, we treated 15 patients suffering from severe RLS, who had previously experienced an augmentation of symptoms under long-term treatment with L-dopa, in an open clinical trial with pergolide. All patients reported an improvement of their RLS symptoms. Our study shows that pergolide, if administered at a mean dose of 0.4 mg in combination with domperidone, is a very effective drug in the treatment of sleep disturbances and daytime symptoms associated with RLS, and does not cause any serious side effects during the observation period of 6 months.

Aged↗
PubMed2002

Restless legs syndrome and periodic limb movement disorder.

Restless leg syndrome and PLMD are nocturnal movement disorders associated with significant adverse effects on the health and well-being of patients and their families [66]. Although the pathophysiological basis remains to be fully described, current research points to abnormalities in CNS function and neurotransmitter systems. The accurate diagnosis of RLS and PMD requires a thorough history, physical examination, diagnostic tests, and often, a referral to a sleep disorders specialist. Considering the prevalence of these conditions and their negative impact, nurses should be well-versed in the assessment and management of these problems as well as in the appropriate education of patients and their families. Nursing research is greatly needed, particularly with regard to the development and testing of biobehavioral interventions designed to decrease associated symptoms and improve clinical outcomes. Finally, because of the complexity of the clinical presentation of RLS and PLMD, this population of patients presents nurse clinicians and researchers alike with an extraordinary opportunity for interdisciplinary collaboration.

Diagnosis, Differential↗
PubMed1990

Effects of the enkephalinase inhibitor SCH 34826 on the sleep-waking cycle and EEG activity in the rat.

The sedative effect of SCH 34826, an enkephalinase inhibitor, was evaluated by studying electroencephalographic (EEG) activity, behaviour and the sleep-waking cycle in the rat. The reference opioid, morphine, was used for comparison. After administration of morphine (10 mg/kg s.c.) the rats were motionless and stuporous at first and then hyperactive. An increase of slow wave sleep, at the expense of both wakefulness and REM sleep was recorded, with high-amplitude slow wave bursts appearing in the EEG tracings during the waking, albeit stuporous, phase. Relative spectral power in the 1-4 and 12-16 Hz bands was increased and there was a shift of the dominant frequency to a lower frequency. The specific opioid antagonist, naltrexone, readily reversed most of these effects. The drug SCH 34826 (10-100 mg/kg p.o.) had no effect on the parameters examined; large doses (300 and 1000 mg/kg p.o.) induced restlessness in some animals, resulting in increased waking. This effect was antagonized by naltrexone. The data indicate that SCH 34826, at doses far greater than those proposed for clinical use, is devoid of sedative liability and does not induce any of the behavioural or EEG effects typical of morphine.

Animals↗
PubMed1999

Treatment of periodic leg movements with a dopaminergic agonist in subjects with total spinal cord lesions.

OBJECTIVE: To investigate the effect of L-dopa on the PLM/h index of spinal cord injured subjects. SETTING: São Paulo, Brazil. METHODS: Thirteen male volunteers with spinal cord section between T7 - T12, and mean age of 31.6+/-8.3 years participated in the study. L-dopa or placebo were administered for 30 days, 1 h before the volunteers went to sleep, in a double blind, crossover design. Polysomnographic recordings were performed on ten occasions: Phase 1: Basal night, following an adaptation night at the sleep laboratory; phase 2: after 1, 7, 21 and 30 days of L-dopa administration; phase 3: first night of L-dopa or placebo withdrawal; phase IV: 1, 7, 21 and 30 days after placebo ingestion. RESULTS: The index of PLM/h on the first night of L-dopa or placebo withdrawal (phase III) was lower than on both the basal night and the first night of L-dopa treatment. At the time of polysomnographic analysis, volunteers were divided into two groups: index of PLM/h below five and those whose index was above five. Comparison between L-dopa and placebo treatments revealed that only those volunteers with an index above five revealed a reduction in PLM in L-dopa. CONCLUSION: These results indicate that despite the spinal cord lesions, L-dopa treatment is capable of minimizing PLM during sleep.

Adult↗
PubMed2006

Management of restless legs syndrome in patients on dialysis.

Restless legs syndrome (RLS) is characterised by an urge to move the legs, uncomfortable sensations in the legs and worsening of these symptoms during rest with at least temporary relief brought on by activity. RLS occurs in 3-15% of the general population and in 10-30% of patients on maintenance dialysis. RLS may lead to severe sleep onset or maintenance insomnia, and greatly impaired quality of life. Current recommendations suggest dopaminergic therapy (levodopa or dopamine receptor agonists: pramipexol, ropinirole, pergolide or cabergoline) as the first-line treatment for RLS. This group of medications is effective in reducing RLS symptoms in the general population; limited information is available on the effect of these drugs in patients with renal failure. However, it must be noted that most published studies in uraemic patients had short treatment periods and insufficient statistical power because of small sample size. Frequent adverse effects of levodopa, seen mainly with continuous use, may limit its use significantly. Rebound and augmentation, problems relatively frequently seen with levodopa, seem to be less prevalent with the use of dopamine receptor agonists, although properly designed comparative trials are still needed to address this question. Alternative treatment options for RLS are gabapentin, benzodiazepines and opioids. For all of these medications, there are only very limited data available on their effectiveness and safety profile in patients on maintenance dialysis. Referral to a specialist for RLS management should be considered for patients with refractory RLS.

Amines↗
PubMed2003

Cabergoline is an effective single-drug treatment for restless legs syndrome: clinical and actigraphic evaluation.

STUDY OBJECTIVES: To evaluate the efficacy and the safety of cabergoline, a dopamine-receptor agonist with a long half-life, in restless legs syndrome (RLS). DESIGN: A 2 month, single blind, open labeled clinical trial. Patients were evaluated with polysomnography at baseline (B), following 1 week of placebo (T0), and after 1 week (T1) and 2 months (T2) of cabergoline treatment. The clinical global impression was assessed using International RLS Study Group Rating Scale and nocturnal actigraphy. SETTING: Sleep Disorders Center. PATIENTS: Twelve patients with moderate to severe RLS (mean age 56.6 years) who were naive to treatment with dopaminergic agents. INTERVENTIONS: Upward titration of cabergoline (from 0.5 mg to 2 mg) in a single evening dose. MEASUREMENTS AND RESULTS: Ten patients completed the study (mean dose, 1.1 mg), and all showed an improvement of RLS symptoms. The results from the International RLS Study Group Rating Scale showed similarities between B (24.3+/-2.9) and T0 (23.1+/-5.9; P=0.6), with significant improvement at T1 (12.5+/-6.0; P=0.01 vs B and T0) and T2 (9.8+/-6.9; P=0.001 vs B and P=0.005 vs T0). The mean nocturnal activity value measured by actigraphy during week 1 decreased from T0 (19.8+/-9.3) to T1 (13.6+/-6.4) and dropped significantly at T2 (8.5+/-5.3; P=0.05). Nine patients continued the treatment up to 12 months with consistent efficacy, few side effects, and no augmentation. CONCLUSIONS: Low doses of cabergoline showed effectiveness and safety in patients with moderate to severe RLS, with no appearance of augmentation phenomenon. Double blind, crossover, polysomnographic studies are necessary to confirm this preliminary data.

Adult↗