Ropinirole for restless legs syndrome

Restless legs syndrome (RLS) is a common and underdiagnosed condition that results in a desire to move the extremities often associated with paresthesia/dysesthesia, motor restlessness, worsening of symptoms at rest with at least temporary relief by activity, and worsening of symptoms in the evening or night. We tested the new dopamine agonist ropinirole in 16 patients with RLS in an open-label trial. The mean daily dose was 2.8+/-2.3 mg (range, 0.5-12.0). The 13 patients who completed the study reported a 58.7% improvement (p = 1.08 x 10(-8)) as judged by the abbreviated International Restless Legs Study Group questionnaire. Three patients discontinued the medication secondary to adverse events (rash and nervousness) and other extenuating circumstances. These encouraging preliminary results justify larger and more controlled trials of ropinirole in patients with RLS.     

Parasomnias including the restless legs syndrome

The three states of mammalian being, W, REM sleep, and NREM sleep, are not mutually exclusive, and may occur simultaneously, oscillate rapidly, or appear in dissociated or incomplete form to produce primary sleep parasomnias. In addition, dysfunctions of a wide variety of organ systems may take adwide variety of organ systems may take advantage of the sleeping state to declare themselves, resulting in secondary sleep parasomnias. Contrary to popular opinion, the majority of the often bizarre and frightening experiences are not the manifestation of underlying psychological or psychiatric conditions. There is an interesting interaction between sleep-disordered breathing and parasominas. Formal study in an experienced sleep disorders center will usually reveal a diagnosable and treatable condition that explains the spells. Continued study of unusual sleep-related events undoubtedly will reveal more fascinating conditions, expanding our knowledge of sleep physiology, and strengthening the bonds between clinicians and basic-science sleep researchers.     

Evidence of peripheral axonal neuropathy in primary restless legs syndrome

The aim of this study was to assess the risk and prognostic factors of gut perforation after orthotopic liver transplantation in children with biliary, atresia using univariate and stepwise regression analysis. Among 51 pediatric recipients who underwent transplantation because of biliary atresia after failure of portoenterostomy, 10 patients (20%) had 19 episodes of gut perforations after 14 transplantations. The median delay between transplantation and perforation was 13 days. These perforations were treated either by suture (n = 21) or ostomy (n = 11). The study of preoperative and perioperative variables showed that children with gut perforation were in surgery for a significantly longer period of time including a longer period of receiving hepatectomy and undergoing portal venous clamp. These children also needed large amounts of blood transfused during hepatectomy. After transplantation there was no difference regarding total steroid doses and early occurrence of cytomegalovirus disease between the two groups. Stepwise regression analysis identified three factors associated with the occurrence of gut perforation: duration of transplant operation, posttransplant intra-abdominal bleeding requiring reoperation, and early portal vein thrombosis. During the postoperative course, severe fungal infections were significantly more frequent in the gut perforation group. The 3-year patient survival rate was 70% in the group with gut perforation and was not different from the group without perforation (80%). This study shows that children with previous portoenterostomy carry a high risk of developing gut perforation after liver transplantation. This is especially true for those patients with the most difficult hepatectomies, which are responsible for the iatrogenic injury of the bowel. Other risk factors pointed out in this study were splanchnic congestion in case of prolonged portal venous clamp time or early portal vein thrombosis and repeated trauma of the bowel caused by reoperations. On the other hand, other well known risk factors, such as steroid therapy and viral diseases, were not involved in the occurrence of gut perforations in this study. Besides emergent surgical treatment, this type of complication requires aggressive therapy against fungal infections.     

Encouraging initial response of restless legs syndrome to pramipexole

Restless legs syndrome (RLS) is a common condition that results in uncomfortable sensations and an urge to move the limbs. Two centers tested a new dopamine agonist, pramipexole, in 23 patients with RLS in a time-limited, open-label, clinical trial. After 4 weeks or more, 19 patients reported significant improvement as assessed by the short International Restless Legs Syndrome Study Group questionnaire (p < 0.0001). These encouraging preliminary results justify larger, controlled trials for pramipexole in patients with RLS.     

Effect of pramipexole in treatment of resistant restless legs syndrome

When atherosclerotic plaques develop, the cross-sectional area of the artery at that point often increases to accommodate the plaque without any reduction in lumen size. In consequence the angiogram does not detect a high proportion of atherosclerotic plaques. The increase in size of the artery (compensatory dilatation-arterial remodelling) varies widely in degree between different plaques even in the same artery. Dilatation of a degree to prevent any loss of lumen size is regarded as adequate compensatory dilatation. In contrast, other plaques are associated with no or minimal increase in the vessel cross-sectional area and a reduction in lumen size in present (inadequate compensation). High-grade stenosis is in particular associated with a total failure of remodelling. Such plaques may have had a rapid growth phase, out-pacing the ability of the medial smooth muscle cells to undergo a rearrangement. The phenomenon of remodelling has important consequences for pathologists who use the traditional method of comparing the lumen size relative to the cross-sectional area of the vessel at the site of a plaque to measure stenosis. The area of the vessel at this point may be anything up to 60% above its size before the plaque developed. An error is introduced which on average overestimates diameter stenosis by 30% when compared to an angiographic equivalent method in which the lumen size at the lesion is compared to the lumen size at an adjacent segment of artery without a plaque.     

Clonazepam: benzodiazepine therapy for the restless legs syndrome

Clonazepam is one of several agents used for the treatment of the restless legs syndrome of ESRD. The drug's pharmacokinetic profile demonstrates safety in patients with altered kidney function. Future studies may provide an enhanced understanding of the physiological basis of the disorder to lead to improved pharmacological therapy. Other medication alternatives such as narcotics, dopamine agonists, clonidine, and gabepentin are available for patients unable to tolerate or receive benefit from clonazepam.     

Periodic limb movement disorder and restless legs syndrome in children with attention-deficit hyperactivity disorder

Sleep disruption can lead to symptoms of attention-deficit hyperactivity disorder (ADHD) in children. Since periodic limb movement disorder and/or restless legs syndrome can cause sleep disruption, we assessed whether these two specific sleep disorders are likely to occur in children with ADHD. We asked a series of 69 consecutive parents of children with ADHD questions about the symptoms of periodic limb movement disorder. Based on a positive response to these periodic limb movement disorder queries, 27 children underwent all-night polysomnography. Eighteen children (aged 2 to 15 years) of the 27 (26% of the 69 children with ADHD) had 5 or more periodic leg movements in sleep per hour of sleep and had complaints of sleep disruption, thus fulfilling the criteria for periodic limb movement disorder. A comparably age- and sex-matched group of children referred to a sleep laboratory for sleep complaints but without ADHD showed only a 5% prevalence (2 of 38 subjects) of periodic leg movements in sleep (P=.017). Eight of the 18 children with ADHD and periodic limb movement disorder and one of the two control patients with periodic limb movement disorder had both a personal and parental history of restless legs syndrome symptomatology. This study further documents the occurrence of periodic limb movement disorder and restless legs syndrome in children and is the first large-scale study establishing a possible comorbidity between ADHD and periodic limb movement disorder. We propose that the sleep disruption associated with periodic limb movement disorder and restless legs syndrome and the motor restlessness of restless legs syndrome while awake could contribute to the inattention and hyperactivity seen in a subgroup of ADHD-diagnosed children.     

A controlled study of additional sr-L-dopa in L-dopa-responsive restless legs syndrome with late-night symptoms

OBJECTIVE: To investigate whether a combination treatment of regular-release levodopa (rr-L-dopa) and sustained-release levodopa (sr-L-dopa) compared with monotherapy of rr-L-dopa improves sleep quality and reduces periodic limb movements (PLM) in patients with restless legs syndrome (RLS) and problems with maintaining sleep. BACKGROUND: Reappearance of RLS symptoms during the second half of the night while being treated with rr-L-dopa is a common problem in the treatment of sleep disturbances caused by RLS. METHODS: A randomized, controlled, double-blind crossover trial was undertaken. Eligible patients fulfilled the diagnostic criteria of the International RLS Study Group, and met an actigraphically confirmed higher number of PLM per hour time in bed (PLM index) during the second half compared with the first half of the night under treatment with rr-L-dopa. During the crossover periods the patients received 100 to 200 mg rr-L-dopa plus either placebo or 100 to 200 mg sr-L-dopa at bedtime for 4 weeks each period. RESULTS: Thirty patients with RLS (11 men and 19 women) were assessed by actigraphy and subjective sleep quality, and showed a significant improvement in PLM index (p < 0.0001), in "time in bed without movements" (p < 0.0001), and in subjective sleep quality (p < 0.001). Eight of 30 patients reported an altered pattern of RLS symptoms, characterized by a time shift of RLS symptoms into the afternoon or evening, five of these during monotherapy with rr-L-dopa. CONCLUSIONS: A combination therapy of rr-L-dopa and sr-L-dopa is better than monotherapy with rr-L-dopa in reducing the frequency of PLM and problems maintaining sleep, even in patients who are severely affected.     

Circadian rhythm of periodic limb movements and sensory symptoms of restless legs syndrome

The symptoms of restless legs syndrome (RLS) worsen while patients are sitting or lying and also worsen at night. The current study was designed to determine if the periodic limb movements (PLMs) and sensory symptoms of RLS are modulated by an independent circadian factor. We recorded sleeping and waking PLMs and waking sensory symptoms in eight volunteers with RLS for 3 successive nights and days, starting with a polysomnographic recording of 2 nights, followed by a third night of sleep deprivation and the day after sleep deprivation. This study showed that both the PLMs and sensory symptoms were worst at night with a maximum for both between midnight and 1:00 AM and a minimum between 9:00 and 11:00 AM. Sleep and drowsiness had a tendency to worsen PLMs and sensory symptoms after the night of sleep deprivation. Circadian temperature curves were normal in all four patients with adequate data collection. The highest PLM counts occurred on the falling phase of the circadian temperature curve whereas the lowest PLM counts occurred on the rising phase of the curve. We conclude that the PLM and sensory symptoms in RLS are influenced by a circadian rhythm, and that the "worsening at night" criterion of the RLS Definition Criteria is, at least in part, distinct from the "worsening while lying or sitting" criterion.     

Polysomnographic and subjective sleep predictors of alcoholic relapse

Previous studies indicate that subjectively reported and objectively measured sleep abnormalities at baseline can increase the risk of relapse in treated alcoholics. However, previous studies did not include both subjective and objective sleep measures in the same group of patients. We utilized polysomnography and the Sleep Disorders Questionnaire to determine if baseline polysomnography increased the ability to predict relapse beyond the prediction with subjective measures alone, after controlling for nonsleep variables that were associated with relapse. We followed 74 patients with a DSM-III-R diagnosis of alcohol dependence, of whom 36 relapsed to at least some drinking during an average follow-up interval of 5 months. Univariate analyses revealed that relapsed patients did not differ from abstinent patients at baseline in demographics or psychiatric co-morbidity, but they had more prior treatment episodes for alcoholism, more difficulty falling asleep, more complaints of abnormal sleep, and, on polysomnography, longer sleep latencies, shorter rapid eye movement sleep latencies, and less stage 4 sleep percentage than abstinent patients. With a series of logistic regression analyses, which controlled for age and gender, we demonstrated that sleep measures improved the prediction model compared with nonsleep variables alone, and that polysomnography-measured sleep latency was the most significant predictor variable. We conclude that subjective and objective measures of baseline sleep are predictors of relapse in treated alcoholic patients. These data also suggest that neurophysiological dysfunction contributes strongly to the etiology of relapse. Finally, sleep disturbance warrants clinical attention as a target of alcoholism treatment.     

Sleep disturbance in spinocerebellar ataxias: is the SCA3 mutation a cause of restless legs syndrome?

OBJECTIVE: We sought to determine possible technical causes of inconclusive results on CT-guided core biopsies of lesions suggestive of malignancy and to determine the frequency with which such lesions are eventually found to be malignant. MATERIALS AND METHODS: We retrospectively reviewed 116 consecutive CT-guided thoracic and abdominal core biopsies performed with a 20-gauge automatic biopsy system. Biopsy results were conclusive (n = 94) if pathology confirmed malignancy and inconclusive (n = 22) if pathology results were negative for malignancy or were nondiagnostic. Lesion volume, location, number of cores, and biopsy technique (paraxial or coaxial) were compared for the conclusive and inconclusive biopsy results. Malignancy within the group of inconclusive biopsy results was determined from a second biopsy, radiographic follow-up, or surgery. RESULTS: Regression analysis identified only the biopsy method as a significant factor affecting biopsy outcome: The paraxial method was more likely to yield a conclusive result than the coaxial method (p < .002). For the two biopsy methods, lesions had similar volumes, locations, and numbers of cores obtained. For single core biopsies, both methods were equivalent. However, if two or more cores were obtained, a conclusive result was achieved in more than 90% of biopsies with the paraxial method versus 65% for the coaxial method. On follow-up, results of 14 (64%) of 22 inconclusive biopsies were malignant, indicating an overall false-negative rate of 12%. CONCLUSION: CT-guided core biopsy performed with 20-gauge automatic biopsy systems and the paraxial method will yield conclusive results significantly more often than the coaxial method. In the event of inconclusive results, malignancy will exist often enough to warrant follow-up.     

Microarousals in patients with sleep apnoea/hypopnoea syndrome

As medical schools begin to implement their new curricula under the guidance of Tomorrow's Doctors, the authors wish to raise some discussion on the form and content of the special study module (SSM) component. In order to do this they put forward in this paper proposals for an SSM in Medicine and Literature. This course has been designed jointly and will be run concurrently in three Scottish medical schools: Glasgow, Aberdeen and Dundee. Arguments for the course's acceptability to faculties of medicine and to students are discussed and its inclusion in the curriculum in terms of its educational impact, skills training, effect on personal development and broadening of the student's perspective are justified. The course structure, content and assessment procedures are described and a reading list proposed. The General Medical Council points out that SSMs should be seen as opportunities for innovation and this course demands a different educational approach from the standard objectives-led approach of most medical education. A process-led model is more appropriate as it stresses the way that students develop while taking the course rather than the end point reached at its finish.     

Pulmonary hypertension in patients with obstructive sleep apnea syndrome

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is associated with an increased cardiovascular morbidity, including pulmonary hypertension. Little is known about factors influencing the degree of pulmonary hypertension and left ventricular dysfunction in patients with OSAS, especially in the absence of concomitant lung disease. METHODS: Right heart catheterization, arterial blood gas analysis, and pulmonary function tests were performed in 92 consecutive patients (81 men and 11 women; mean +/- SD age, 53.1 +/- 11.0 years) with polysomnographically verified OSAS, in whom clinically significant lung disease was excluded. RESULTS: Eighteen patients (20%) had mild pulmonary hypertension; 8 (44%) of them also had increased pulmonary capillary wedge pressures (Ppew). Left ventricular dysfunction was associated with arterial hypertension. Only Ppcw (r = 0.51; P < .001) and the percentage of time during sleep spent with an oxygen saturation below 90% (as an indicator of the severity of OSAS) (r = 0.34; P = .003) were significantly and independently associated with pulmonary artery pressure. CONCLUSIONS: Obstructive sleep apnea syndrome can cause mild pulmonary hypertension, even in the absence of pulmonary disease. In these patients, pulmonary hypertension is of the postcapillary type, or-in patients with normal left ventricular function-strongly related to the severity of OSAS. Our findings indicate that OSAS may constitute an important, and independent, risk factor for pulmonary hypertension.     

Polysomnographic sleep is not clinically impaired in Vietnam combat veterans with chronic posttraumatic stress disorder

BACKGROUND: Because sleep is typically disturbed in posttraumatic stress disorder (PTSD), this study was undertaken to evaluate a group of Vietnam combat veterans with the disorder using clinical polysomnographic techniques. METHODS: Eighteen Vietnam combat veterans with PTSD and 10 healthy non-combat-exposed Vietnam era veterans participated in 2 nights of polysomnographic study and a multiple sleep latency test. RESULTS: No significant differences between subjects and controls were noted except for greater sleep onset latency to stage 2 (p < .03), and lower arousals/hour from stages 3 & 4 (p < .04) on night 2, and lower subjectively estimated total sleep time on night 1 (p < .005) in the case of PTSD subjects. Otherwise, results from the second night served to replicate those from the first, and no significant differences appeared on 2 successive nights for any polysomnographic variable. No daytime hypersomnolence was detected. CONCLUSIONS: Polysomnographically recorded sleep was notably better than expected in the presence of clinically significant PTSD with typical histories of disrupted sleep. In these subjects, there is no clinically significant sleep disorder or typical pattern of sleep disturbance detectable by standard polysomnography.     

Familial painful restless legs syndrome correlates with pain dependent variation of blood flow to the caudate, thalamus, and anterior cingulate gyrus

To understand the relationship of caudate, thalamic, and anterior cingulate perfusion to pain states, we investigated familial restless legs syndrome in a father and daughter during the state of pain induced by immobility using semiquantitative regional cerebral blood flow (rCBF) brain single photon emission computed tomography (SPECT). The father underwent 4 brain SPECT scans using the rCBF tracer 99mTc-HMPAO several weeks apart, at different pain levels and after treatment with L-dopa. Caudate, thalamic, and anterior cingulate rCBF indices were measured. The caudate nuclei showed a 13% reduction in rCBF with increasing pain. The thalami and anterior cingulate showed a 7 and 6.6% increase in rCBF, respectively, with increasing pain. Compared to normal controls at rest, there was a decrease in caudate rCBF by 13% and an increase in thalamic rCBF by 3%. Linear regression for the caudate nuclei revealed a significant reduction in rCBF (p < 0.05), as pain increased. The daughter underwent an identical rCBF brain SPECT scan procedure at a high pain level induced by immobilization. Her scan showed a 12% reduction in caudate rCBF and a 1.2% increase in the anterior cingulate rCBF compared to healthy controls. The study supports the association between pain and decreased regional cerebral blood flow to the caudate nucleus as reported in fibromyalgia syndrome. There is increase in anterior cingulate rCBF with increasing pain. Our findings also corroborate that there is increased thalamic rCBF with pain stimulation.     

Clustering of sleep electroencephalographic patterns in patients with the fibromyalgia syndrome

Several electroencephalographic (EEG) abnormalities have been observed during sleep in patients suffering from the fibromyalgia syndrome (FMS). In this study, 12 patients with fibromyalgia and 14 control subjects had two polysomnographic recordings obtained at home. Data from the second night were subjected to blinded manual scoring as well as signal processing using linked or 'step-wise clustering for pattern recognition. In this procedure, a common learning set was generated using the spectral information in three 2 min EEG samples from each of the sleep stages selected from five patients with FMS and five controls. In this way, 17 characteristic EEG classes were defined. All 2 s EEG segments from the whole night from all subjects were then assigned to one of these classes. Five of the classes (dominated by 0.5-4.5 Hz activity) were more frequent in the control group, whereas three other classes (dominated by 8-11 Hz activity) were prevalent in the patient group. This trend was consistent in all sleep stages, although most striking in non-rapid eye movement (NREM) sleep. The predominance of these classes in the patient group may correspond to the alpha-EEG sleep anomaly previously reported in subjects with FMS. More importantly, as the EEG power in the lowest frequency range (prevalent in controls) probably is a marker for restorative sleep, the findings may reflect important aspects of sleep disturbances n subjects suffering from FMS, thereby contributing to some of the daytime symptoms in these patients.     

Impairment of muscle energy metabolism in patients with sleep apnoea syndrome

Impairment of muscle energy metabolism has been demonstrated in normal subjects with chronic hypoxaemia (altitude chronic respiratory failure). The purpose of this study was to verify the hypothesis that a comparable condition could develop in patients with sleep apnoea syndrome (SAS), considering that they are exposed to prolonged and repeated hypoxaemia periods. Muscle metabolism was assessed in 11 patients with SAS performing a maximal effort on cycloergometer. In comparison with normal subjects, SAS patients reached lower maximal loads [144 +/- 7 vs. 182 +/- 10 W (P < 0.005)] and lower peak oxygen uptakes [26.4 +/- 1.2 vs 33.2 +/- 1.4 ml kg-1 min-1 (P < 0.005)]. Abnormal metabolic features were found: maximal blood lactate concentration was significantly lower than in normal subjects [0.034 +/- 0.004 vs. 0.044 +/- 0.002 mmol l-1 W-1 (P < 0.05)]; and lactate elimination rate, calculated during a 30-min recovery period, was reduced [0.127 +/- 0.017 vs, 0.175 +/- 0.014 mmol l-1 min-1 (P < 0.025)]. The extent of these anomalies correlated with the severity of SAS. The patients also showed higher maximal diastolic blood pressures than normal subjects [104 +/- 5 vs. 92 +/- 4 mmHg (P < 0.05)]. These results can be interpreted as indications of an impairment of muscle energy metabolism in patients with SAS. Decrease in maximum blood lactate concentration suggests an impairment of glycolytic metabolism, while decrease in the rate of lactate elimination indicates a defect in oxidative metabolism. Since no respiratory pathology apart from SAS was found in this group of patients, it seems legitimate to link the genesis of these impairments to repeated bouts of nocturnal hypoxaemia.     

Control of breathing in obstructive sleep apnoea and in patients with the overlap syndrome

In some patients obstructive sleep apnoea (OSA) may co-exist with chronic obstructive pulmonary disease (COPD) and respiratory failure; the so-called "overlap syndrome". Obstructive, hypercapnic patients have both blunted ventilatory and mouth occlusion pressure responses during CO2 stimulation. The purpose of this study was to compare the pattern of breathing and CO2 response between OSA patients and those with the overlap syndrome. Twenty obese men with OSA and normal lung function (Group A), 11 obese men with overlap syndrome (Group B) and 13 healthy nonobese subjects (Group C) were examined. Lung function tests, breathing pattern, mouth occlusion pressure (P0.2) at rest, and respiratory responses during CO2 rebreathing were investigated. Diagnosis of OSA was established by standard polysomnography. There were no statistical differences between Groups A and B in apnoea & hypopnoea index (62 vs 54), mean arterial oxygen saturation (SaO2) during sleep (85 vs 84%) and in body mass index (BMI) 34.3 vs 36.3 kg.m-2. Minute ventilation, mean inspiratory flow and P0.2 at rest were increased in both groups of patients in comparison to controls. During CO2 rebreathing, group A had normal ventilatory and P0.2 responses, similar to controls, (2.7 +/- 1.1 vs 2.1 +/- 0.4 l.min-1.mmHg-1 and 0.7 +/- 0.3 vs 0.71 +/- 0.25 cmH2O.mmHg-1, respectively). However, Group B had significantly decreased ventilatory and P0.2 responses to CO2 (0.71 +/- 0.23 l.min-1.mmHg-1 and 0.34 +/- 0.17 cmH2O.mmHg-1, respectively). This comparison showed that patients with OSA had normal CO2 response when awake, whereas those with overlap syndrome had diminished CO2 response when awake.(ABSTRACT TRUNCATED AT 250 WORDS)