An update on the treatment of Restless Legs Syndrome/Willis-Ekbom Disease: prospects and challenges.

INTRODUCTION: Restless Legs Syndrome/Willis-Ekbom Disease (RLS/WED) is a sleep disorder characterized by an urge to move the legs, frequently associated or triggered by unpleasant sensations in the lower limbs that affects approximately 2.5% of adults. Therapy and management of RLS/WED require long-term interventions, since the typical manifestation of this disorder is chronic. Areas covered: In this review, we provide an update regarding the treatment of RLS/WED with particular attention to future challenges for its management. We reviewed a large variety of treatments studied in clinical trials and supported by the most updated guidelines. Alongside with first-line interventions other pharmacological options including opioids, benzodiazepines, iron therapy, and newly studied drugs are discussed. Furthermore, due to the occurrence of augmentation and worsening of symptoms we also reviewed the development of non-pharmacologic alternatives. Expert commentary: The management of RLS/WED is a challenge because of different long-term issues. Several complications, such as loss of the therapeutic effect of dopaminergic or non-dopaminergic agents and augmentation, are still unsolved concerns. However, the development of new drugs acting on adenosinergic and glutamatergic neurotransmission seems promising. Randomized controlled trials are needed in order to recognize effectiveness of new drugs or non-pharmacological treatment strategies.

National validation and proposed revision of REM sleep behavior disorder screening questionnaire (RBDSQ).

We validated the Italian version of the rapid eye movement sleep behavior disorder (RBD) screening questionnaire (RBDSQ) and calculated its cut-off value for discriminating RBD group from other sleep disorders and healthy controls (HC). 380 patients with sleep disorders and 101 HC were enrolled. RBDSQ achieved an acceptable Cronbach's α value of 0.787 and item 10 was the only one with a very low item-total biserial correlation (0.141). At ROC analysis, we obtained an AUC of 0.888, denoting a good performance of the RBDSQ total score for predicting the RBD status. The optimal cut-off value was 8 and it achieved good values of both sensitivity and specificity (0.842 and 0.780, respectively). Due to the poor performance of item 10 in our sample, we analyzed the RBDSQ without this item (called "revised RBDSQ"). We obtained a good Cronbach's α of 0.802. When evaluating the performance of the revised score in predicting the RBD status, we obtained an increased value of AUC (0.899). The optimal cut-off value was still 8 (sensitivity = 0.829; specificity = 0.820). The Italian version of RBDSQ is a sensitive tool for the identification of RBD patients. An improvement of the instrument could be obtained by removing item 10 and define a higher cut-off value of 8. The "revised RBDSQ" represents a reliable screening questionnaire for primary care physicians and neurologists and its employment may facilitate the choice of subjects that should undergo a PSG that confirms the diagnosis of RBD, thus avoiding polysomnographic exams when not needed.

Obstructive sleep apnea in Prader-Willi syndrome: risks and advantages of adenotonsillectomy.

Obstructive sleep apnea is a well-known clinical manifestation of Prader-Willi syndrome. The aim of our study is to evaluate the efficacy of adenotonsillectomy for the treatment of the disorder as well as the improvement of their post-operative quality of life. Five patients with moderate to severe obstructive sleep apneas and adenotonsillar hypertrophy of grade III-IV underwent adenotonsillectomy. Pre- and postoperative apneas and Quality of Life were assessed respectively with a polysomnography with multi-sleep latency test and with the pediatric Quality of Life questionnaire, performed before and 6 months after surgery. A decrease of apnea/hypopnea index values has been detected between pre- and post-surgery (t=2.64, P=0.005), as well as oxygen desaturation index values (t=5.51, P=0.005), multi-sleep latency test (t=4.54, P=0.01), and of the values of pediatric Quality of Life questionnaire. No correlation has been detected between body mass index and apnea/hypopnea index, oxygen desaturation index and multi-sleep latency test values pre- and post-adenotonsillectomy. A correlation has been found between multi-sleep latency test and oxygen desaturation index values post-surgery (P=0.04). No post-operative complications were observed. Our data underline the efficacy of surgery in Prader-Willi patients with adenotonsillar hypertrophy in order to improve their quality of life.

Risk factors for neurodegeneration in idiopathic rapid eye movement sleep behavior disorder: a multicenter study.

OBJECTIVE: To assess whether risk factors for Parkinson disease and dementia with Lewy bodies increase rate of defined neurodegenerative disease in idiopathic rapid eye movement (REM) sleep behavior disorder (RBD). METHODS: Twelve centers administered a detailed questionnaire assessing risk factors for neurodegenerative synucleinopathy to patients with idiopathic RBD. Variables included demographics, lifestyle factors, pesticide exposures, occupation, comorbid conditions, medication use, family history, and autonomic/motor symptoms. After 4 years of follow-up, patients were assessed for dementia or parkinsonism. Disease risk was assessed with Kaplan-Meier analysis, and epidemiologic variables were compared between convertors and those still idiopathic using logistic regression. RESULTS: Of 305 patients, follow-up information was available for 279, of whom 93 (33.3%) developed defined neurodegenerative disease. Disease risk was 25% at 3 years and 41% after 5 years. Patients who converted were older (difference = 4.5 years, p < 0.001), with similar sex distribution. Neither caffeine, smoking, nor alcohol exposure predicted conversion. Although occupation was similar between groups, those who converted had a lower likelihood of pesticide exposure (occupational insecticide = 2.3% vs 9.0%). Convertors were more likely to report family history of dementia (odds ratio [OR] = 2.09), without significant differences in Parkinson disease or sleep disorders. Medication exposures and medical history were similar between groups. Autonomic and motor symptoms were more common among those who converted. Risk factors for primary dementia and parkinsonism were generally similar, except for a notably higher clonazepam use in dementia convertors (OR = 2.6). INTERPRETATION: Patients with idiopathic RBD are at very high risk of neurodegenerative synucleinopathy. Risk factor profiles between convertors and nonconvertors have both important commonalities and differences.

Italian recommendations on dental support in the treatment of adult obstructive sleep apnea syndrome (OSAS).

BACKGROUND: The aim of the present article is to present a set of proposed clinical recommendations aimed at Italian dentists involved in the management of patients with obstructive sleep apnea syndrome or snoring. METHODS: With the purpose of creating a study group, some of the most important Italian scientific societies operating in fields relevant to the issue of sleep medicine in dentistry were asked to appoint a representative. Each member of the study group was required to answer questions regarding the clinical management of OSAS and snoring. RESULTS: Oral appliances can be used to treat: - simple snoring, in patients who do not respond to, or do not appear to be suitable candidates for behavioral measures such as weight loss or positional therapy; - mild or moderate OSAS, in patients who prefer OAs to continuous positive airway pressure (CPAP) or who are not suitable candidates for CPAP, because of its failure or failure of behavioral approaches like weight loss or positional therapy; - severe OSAS, in patients who do not respond to or do not tolerate CPAP and in whom no indication for either maxillofacial or ENT surgery appears applicable. CONCLUSIONS: The application of oral appliances is highly desirable in cases of simple snoring or mild to moderate OSAS, whereas considerable caution is warranted when treating severe OSAS. It is fundamental to ensure that the patient understands his problem and, at the same time, to present all the various treatment options.

Comorbidity and medication in REM sleep behavior disorder: a multicenter case-control study.

OBJECTIVE: This controlled study investigated associations between comorbidity and medication in patients with polysomnographically confirmed idiopathic REM sleep behavior disorder (iRBD), using a large multicenter clinic-based cohort. METHODS: Data of a self-administered questionnaire on comorbidity and medication use of 318 patients with iRBD and 318 matched controls were analyzed. Comparisons between cases and controls were made using logistic regression analysis. RESULTS: Patients with iRBD were more likely to report depression (odds ratio [OR] 2.0, 95% confidence interval [CI] 1.3-2.9) and concomitant antidepressant use (OR 2.2, 95% CI 1.4-3.6). Subanalysis of antidepressant agents revealed that the increased use of antidepressants in iRBD was due to selective serotoninergic reuptake inhibitors (OR 3.6, 95% CI 1.8-7.0) and not due to other antidepressant classes. Patients with iRBD reported more lifetime antidepressant use than comorbid depression (antidepressant use: OR 1.9, 95% CI 1.1-3.3; depression: OR 1.6, 95% CI 1.0-2.5). Patients with iRBD reported more ischemic heart disease (OR 1.9, 95% CI 1.1-3.1). This association did not change substantially when adjusting for cardiovascular risk factors (OR 2.3, 95% CI 1.3-3.9). The use of inhaled glucocorticoids was higher in patients with iRBD compared to controls (OR 5.3, 95% CI 1.8-15.8), likely reflecting the higher smoking rate in iRBD (smoking: OR 15.3, 95% CI 2.0-118.8; nonsmoking: OR 2.4, 95% CI 0.4-13.2) and consequent pulmonary disease. CONCLUSIONS: This large study confirms the association between comorbid depression and antidepressant use in iRBD. In addition, there was an unexpected association of iRBD with ischemic heart disease that was not explained by cardiovascular risk factors.

Restless legs syndrome as the presenting symptom of multiple myeloma.

We report a patient affected by restless legs syndrome as the presenting symptom of multiple myeloma, a hematologic malignancy characterized by clonal proliferation of plasma cells in the bone marrow and monoclonal immunoglobulin in the blood and/or urine.

Defining the borders between Sleep-Related Eating Disorder and Night Eating Syndrome.

OBJECTIVES: Nocturnal eating is a common symptom of two clinical conditions with different pathogenesis and needing different therapeutic approaches: Sleep Related Eating Disorder (SRED) and Night Eating Syndrome (NES). The first is considered a parasomnia while the second is an eating disorder; however, the distinction between SRED and NES is still a controversial matter. The aim of this study was to better define psychological, behavioral, and polysomnographic characteristics of the two syndromes. METHODS: An eating disorders' specialist tested a group of 28 nocturnal eaters diagnosed as affected by SRED by a sleep expert, following the current criteria of the international classification of sleep disorders, to find out if any of them was affected by NES according to the criteria suggested by both sleep and eating disorders specialists during the first international meeting on Night Eating Syndrome (Minneapolis, 2009) and if they had specific psychological or polysomnographic characteristics. RESULTS: Twenty-two subjects were diagnosed to be affected by NES. They scored higher on the physical tension subscale of the Sleep Disturbance Questionnaire (SDQ) and on the mood and sleep subscale of the Night Eating Questionnaire (NEQ), but there were no other significant differences between SRED and NES patients nor for age, Body Mass Index (BMI), or gender distribution. CONCLUSIONS: The overlap between the symptomatology and the polysomnographic characteristics of the two pathologies and the difficulty in making a differential diagnosis between NES and SRED indicate the need for an update of the diagnostic criteria for SRED, as was recently done for NES.