Quality of life among patients with restless legs syndrome: A systematic review and meta-analysis.

OBJECTIVE: The primary aim was to estimate the pooled mean score of quality of life (QoL) (total, mental and physical health components) among patients with Restless Legs Syndrome (RLS). Secondary aims were to assess: (I) QoL differences for RLS vs. control groups, (II) heterogeneity and possible sources; and (III) moderating variables. METHODS: Studies identified in PubMed, Scopus, Web of Science, and ProQuest between January 2000 and December 2022 were included. Methodological quality was assessed with Newcastle Ottawa Scale. The protocol was pre-registered (PROSPERO, CRD42023387318). RESULTS: Twenty-seven studies (20121 participants, 12 countries) were included. The corrected pooled estimated mean score of QoL was 47.92 (27 studies, CI 95 %: 43.11 to 52.72, range 0-100, i.e., low-high QoL) and was marginally affected by publication year (increased 0.89 by each year, p = 0.12). The corrected pooled estimated mean score of the mental health component was 47.32 (17 studies, 95 % CI: 43.12 to 51.51, range 0-100) and influenced by RLS instrument (decreased with recent versions, p = 0.05). The corrected pooled estimated mean score of the physical health component was 39.08 (17 studies, 95 % CI: 33.05 to 45.10, range 0-100), with no statistically significant moderator. The pooled estimated QoL scores were statistically significantly lower in RLS patients compared to control groups with standardized mean difference (SMD) of -0.78, -0.57 and -0.50 respectively for overall QoL (24 studies), physical and mental health components (14 studies). Total QoL SMD was affected by proportion of women. CONCLUSION: Low QoL was revealed among RLS patients, which was statistically significantly reduced compared to control groups.

Restless legs syndrome in patients with obstructive sleep apnea: Association between apnea severity and symptoms of depression, insomnia, and daytime sleepiness.

OBJECTIVE: To determine if the prevalence and severity of restless legs syndrome (RLS) varies with apnea severity and analyze differences between the sexes in terms of comorbid RLS with symptoms of depression, insomnia, and daytime sleepiness in patients with obstructive sleep apnea (OSA). METHODS: Symptoms of depression, insomnia, and daytime sleepiness were defined as Patient Health Questionnaire-9 score ≥10, Insomnia Severity Index score ≥15, and Epworth Sleepiness Scale score ≥11. Multivariate logistic and linear regression analyses were conducted. RESULTS: In 707 adults with OSA (85.1% males), 16.1% (n = 114) had comorbid RLS. The prevalence of RLS was markedly lower in those with moderate and severe OSA than in those with mild OSA. Similarly, the odds of RLS significantly decreased with increasing apnea-hypopnea index. After controlling for age and sex, in patients with comorbid RLS, the International RLS Study Group Rating Scale scores were negatively correlated with apnea-hypopnea index and a nadir peripheral oxygen saturation during sleep. The presence of RLS was more likely to be associated with symptoms of depression, insomnia, and daytime sleepiness after controlling for confounding variables, but only in men. CONCLUSIONS: RLS is frequently noted in combination with OSA, with a female preponderance. The severities of OSA and RLS may be negatively associated. In patients with OSA, sex-related differences in terms of comorbid RLS with symptoms of depression, insomnia, and daytime sleepiness warrant further investigations.

Coexistence of periodic limb movements during sleep with restless legs syndrome and its association with hypertension in Japanese patients.

BACKGROUND: Caucasian patients with restless legs syndrome (RLS) frequently exhibit periodic limb movements during sleep (PLMS), which may increase the risk of hypertension. We evaluated the positivity rate of PLMS and factors associated with positivity in Japanese patients with RLS, and tested whether the complications of PLMS are associated with the presence of hypertension. METHODS: We retrospectively investigated polysomnographic data and the presence or absence of hypertension in patients with RLS. Patients with systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg or those taking antihypertensive medication were categorized as the group with hypertension. RESULTS: Among 468 patients, 200 (42.7%) had periodic limb movement index (PLMI) values ≥ 15/h and 108 (23.1%) met the criteria of positivity for hypertension. Multiple logistic regression analysis revealed that only higher age was significantly associated with PLMI values ≥ 15/h. Multiple linear regression analyses of factors associated with an increased PLMI also showed that increased PLMI was significantly correlated with higher age and male sex, but not with the international restless legs scale scores. Multiple logistic regression analysis also revealed that higher age and body mass index, not PLMI values ≥ 15/h, were significantly associated with the presence of hypertension. CONCLUSION: The PLMS-positivity rate may be lower in Japanese patients with RLS than in Caucasian patients, and it increases with age and male sex, but not with the severity of the disorder. Furthermore, PLMS complications were not associated with the risk of hypertension in Japanese patients with RLS.

Chronic dizziness in restless legs syndrome (RLS) patients responsive to levodopa or dopamine agonists.

Apart from the legs, restless legs syndrome (RLS) also affects the arms, head, neck, face, oral cavity, genital area, abdomen, intestines and bladder. RLS is also linked to several comorbid diseases, including headache disorders. Its association with dizziness has never been explored. We are reporting on two patients with RLS who also had a history of chronic dizziness. The treatment with levodopa or dopamine agonists completely alleviated both RLS and dizziness. We propose that RLS-like symptoms in the head may be experienced as dizziness and that dizziness may be part of the symptom complex of RLS. A large number of patients with chronic dizziness remain undiagnosed in clinical practice. We suggest exploring the history of RLS in patients presenting with chronic dizziness. Such patients may respond to levodopa or dopamine agonists. Because the response was seen in only two patients, a prospective placebo-controlled trial is needed to confirm these findings.

Restless leg syndrome as a complication of primary hyperparathyroidism: insights from a retrospective study.

INTRODUCTION: Restless leg syndrome (RLS) is an invalidating neurological disorder with a complex, largely unknown pathophysiology. While RLS is observed in Parkinson's disease and in renal failure, idiopathic cases are common. Limited reports associate RLS with parathyroid hormone (PTH). This study analyzes a cohort of patients with primary hyperparathyroidism (PHPT) and chronic post-surgical hypoparathyroidism (hypo PTH), to investigate RLS prevalence, and associated risk factors. METHODS: Ninety-five patients (54 PHPT, 41 hypo PTH) were consecutively enrolled at the bone metabolism outpatient clinic. The revised IRLSSG diagnostic criteria were used to diagnose RLS, with assessments conducted through face-to-face interviews and neurological examination. When RLS was confirmed, the RLS severity scale was applied. Retrospective records included calcium-phosphate metabolism-related parameters, surgery details, renal lithiasis, fragility fractures, and densitometric features (T-score). RESULTS: RLS was diagnosed in 22.2% PHPT patients, compared to 4.9% of patients with hypo PTH (p = 0.02). Of RLS diagnosed patients, 91.7% had a history of parathyroidectomy, compared to 47.6% of patients without RLS (p = 0.01). Most of the operated patients reported that surgery determined an improvement of symptoms; however, mean score severity of RLS at our evaluation was 15/40, defined as moderate. PTH and calcium levels were not statistically associated to the presence of RLS. CONCLUSION: Our study suggests that PHPT may be one of the etiologies of RLS. Parathyroidectomy alleviates symptoms in the vast majority of the cases but does not remove them.

Functional recovery after ischemic stroke: Impact of different sleep health parameters.

Sleep disturbances after ischaemic stroke include alterations of sleep architecture, obstructive sleep apnea, restless legs syndrome, daytime sleepiness and insomnia. Our aim was to explore their impacts on functional outcomes at month 3 after stroke, and to assess the benefit of continuous positive airway pressure in patients with severe obstructive sleep apnea. Ninety patients with supra-tentorial ischaemic stroke underwent clinical screening for sleep disorders and polysomnography at day 15 ± 4 after stroke in a multisite study. Patients with severe obstructive apnea (apnea-hypopnea index ≥ 30 per hr) were randomized into two groups: continuous positive airway pressure-treated and sham (1:1 ratio). Functional independence was assessed with the Barthel Index at month 3 after stroke in function of apnea-hypopnea index severity and treatment group. Secondary objectives were disability (modified Rankin score) and National Institute of Health Stroke Scale according to apnea-hypopnea index. Sixty-one patients (71.8 years, 42.6% men) completed the study: 51 (83.6%) had obstructive apnea (21.3% severe apnea), 10 (16.7%) daytime sleepiness, 13 (24.1%) insomnia, 3 (5.7%) depression, and 20 (34.5%) restless legs syndrome. Barthel Index, modified Rankin score and Stroke Scale were similar at baseline and 3 months post-stroke in the different obstructive sleep apnea groups. Changes at 3 months in those three scores were similar in continuous positive airway pressure versus sham-continuous positive airway pressure patients. In patients with worse clinical outcomes at month 3, mean nocturnal oxygen saturation was lower whereas there was no association with apnea-hypopnea index. Poorer outcomes at 3 months were also associated with insomnia, restless legs syndrome, depressive symptoms, and decreased total sleep time and rapid eye movement sleep.

Improvement of restless leg syndrome in maintenance hemodialysis patients with limb ischemic preconditioning: a single-center randomized controlled clinical trial.

OBJECTIVE: This study evaluated the efficacy and safety of limb ischemic preconditioning (LIPC) in treating restless leg syndrome (RLS) in maintenance hemodialysis (MHD) patients. METHODS: A total number of 45 patients participated in the study. They were randomly divided into LIPC group and control group. The LIPC was performed by inflating the limb ischemic preconditioning training device in the patient's thigh to 200 mmHg to create transient ischemia, whereas control group inflated the device to 20 mmHg. International Restless Legs Syndrome (IRLS), Clinical Global Impression Scale (CGI-S), and Medical Outputs Study Sleep Scale were employed to evaluate LIPC effectiveness. The primary endpoint was the 'rate of clinical improvement in RLS severity', defined as the percentage of patients who had an IRLS score decrease of ≥5 points in each group. RESULTS: After intervention, the rate of clinical improvement in RLS severity was 56.5% in the LIPC group and 13.6% in the control group (13 (56.5) vs 3 (13.6), p = 0.003). In addition, the LIPC group's IRLS, CGI-S scores, the sleep disturbance and somnolence scores showed a significant downward trend compared to the control group (-5.5 ± 5.3 vs - 1.0 ± 3.8, p = 0.002; -1.7 ± 1.2 vs - 0.5 ± 1.4, p = 0.003; -15.5 ± 17.8 vs 3.7 ± 12.0, p < 0.001; -9.9 ± 18.8 vs - 2.4 ± 8.6, p = 0.003). During the study, there were no serious adverse event in any of the patients. CONCLUSIONS: LIPC could be employed to effectively and safely alleviate the RLS symptoms in MHD patients.

Can restless legs be a sign of something else? A case report of spondyloarthritis presenting with restless legs syndrome and a review of the literature.

Restless legs syndrome (RLS) is a chronic movement disorder characterized by an urge or need to move the limbs, usually associated with uncomfortable sensations in the legs and sleep disorders. In general, two clinical forms of RLS are described: primary and secondary. Although primary RLS has a familial component, the underlying mechanism is still not fully understood but seems to be related to abnormalities in the dopaminergic and glutamatergic pathways of the central nervous system. The secondary forms of the syndrome are associated with iron deficiency, renal failure, pregnancy, diabetes mellitus, peripheral neuropathy, and several rheumatologic disorders such as rheumatoid arthritis and Sjögren's syndrome. In a few clinical trials, an increased frequency of RLS has been reported in patients with spondyloarthritis. In this report, a case of coexistence of spondyloarthritis and RLS is presented, showing satisfactory improvement with conservative treatment and additionally adding naproxen. Anemia of chronic disease occurring in rheumatic diseases, and associated iron deficiency may contribute to the development of RLS.

Prevalence and clinical characteristics of sleep disorders in chronic obstructive pulmonary disease: A systematic review and meta-analysis.

BACKGROUND: Sleep disorders, including obstructive sleep apnea (OSA), restless leg syndrome (RLS) and insomnia, are present in chronic obstructive pulmonary disease (COPD) with varied prevalence. The aim of this systematic review and meta-analysis was to investigate prevalence of OSA, RLS and insomnia in patients with COPD and summarize their clinical characteristics. METHODS: We searched PubMed, Web of Science and Scopus for eligible articles reporting the prevalence of OSA, RLS, and insomnia in COPD patients. The Newcastle‒Ottawa scale was applied for quality assessment. Odds ratios or mean differences with 95 % confidence intervals (CIs) were applied for the overall prevalence calculation and clinical characteristics assessment. Sensitivity analysis, subgroup analysis and meta-regression were conducted to evaluate the heterogeneity of the results. RESULTS: Sixty articles reporting the prevalence of sleep disorders in patients with COPD were included, and the prevalence of OSA, RLS, and insomnia reached 29.1 %(95%CI 27.2%-30.9 %), 21.6 %(95%CI 11.8%-33.3 %) and 29.5 %(95%CI 16.9%-44.0 %), respectively. COPD patients with OSA were characterized by male sex (OR 1.631 95 % CI: 1.231-2.161), obesity(kg/m2) (MD 4.435, 95 % CI 3.218-5.652), higher Epworth Sleepiness Scale (MD: 3.741, 95 % CI: 0.655-6.828, p = 0.018), better pulmonary function (MD 5.66, 95 % CI 3.546-7.774) and higher risks of hypertension (OR 1.933 95 % CI 1.382-2.70) and diabetes (OR 1.898 95 % CI 1.264-2.849). COPD patients with RLS were associated with a higher Epworth sleepiness scale (ESS) score (MD 3.444, 95 % CI 1.880-5.008) and a longer COPD duration(year) (MD: 3.656, 95 % CI: 2.209-5.103). COPD patients with insomnia were characterized by female sex(OR 0.556, 95%CI 0.545,0.567, p < 0.001). CONCLUSION: Our study suggests that OSA, RLS and insomnia are common in COPD patients with specific clinical characteristics. Further studies are needed to explore the interactions between COPD and sleep disorders.

The Relationship between Serum Selenium Levels and Restless Leg Syndrome in Chronic Kidney Disease Patients.

Background and Objectives: Chronic kidney disease (CKD) is a global public health issue with rising incidence linked to substantial morbidity and mortality. Selenium, an antioxidant trace element, has been linked to low serum levels in end-stage renal disease. Restless Leg Syndrome (RLS), a sleep disorder, is prevalent in CKD patients and significantly impacts their quality of life. The objective of this study was to examine the correlation between serum selenium levels and the prevalence of restless leg syndrome in individuals with chronic kidney disease. Materials and Methods: Forty-six CKD patients undergoing serum selenium level assessments between 1 January 2020 and 28 February 2022, at the Hitit University Faculty of Medicine Department of Nephrology Outpatient Clinic or Hemodialysis Unit, were included. Patients over 18 years of age with no history of hematological or oncological diseases or acute or chronic inflammatory conditions were included in the study groups. Patients taking selenium supplements were excluded. Demographic data, comorbidities, and laboratory values were collected, and RLS presence and severity were evaluated. Statistical analyses include descriptive statistics, correlation analysis, the Mann-Whitney U test, Student's t test, and Chi-square test. Results: Among the 46 patients, 16 (34.78%) had RLS symptoms. The patient group included 34.78% predialysis, 34.78% peritoneal dialysis, and 30.44% hemodialysis patients, with a median age of 47.98 years. There was no difference in age, gender, and Charlson comorbidity between patients with or without RLS (p = 0.881, p = 0.702, p = 0.650). RLS prevalence varied across CKD subgroups, with hemodialysis patients having a higher prevalence (p = 0.036). Clinical parameters such as blood urea nitrogen, creatinine, calcium, phosphorus, platelet counts, and parathyroid hormone levels exhibited significant differences between patients with and without RLS (p < 0.05). Serum selenium levels were not significantly different between patients with and without RLS (p = 0.327). Conclusions: With an increased comorbidity burden, CKD poses a significant healthcare challenge. When accompanied by RLS, this burden can be debilitating. The difference in CKD stages between groups has shed light on a critical determinant of RLS in this population, emphasizing the role of the chronic kidney disease stage. In our study, serum selenium levels were not associated with the presence and severity of RLS. However, prospective studies with larger numbers of participants are needed to draw a definitive conclusion.

Assessment of Sleep Disturbances on Mental Health in Patients with Restless Legs Syndrome.

Background and Objective: In our study, we aimed to evaluate the sleep disturbances of patients diagnosed with restless legs syndrome (RLS) regarding their mental health according to the severity of the disease. Materials and Methods: The study included 166 patients diagnosed with RLS and 161 healthy controls in the same age interval as patients. Sleep disturbances of patients were defined with the "personal information form" (PIF) prepared by the researchers, while the mental health status of patients was defined with the "Brief Symptom Inventory" (BSI). Results: All RLS patients had an increase in BSI subscale points, with a positive correlation to disease severity, and subscale points were significantly higher than the control group (p < 0.05). Those with the "frequent waking" problem had higher BSI subscale points compared to those without the problem (p<0.01 or 0.001). Those with "waking with respiratory distress," "daytime sleepiness," "very early waking," and "sleep disorder" problems had statistically significantly high BSI subscale points for all subscales, apart from hostility, compared to those without these problems (p<0.01 or 0.001). Conclusion: It is considered that assessment of sleep disturbances causing disrupted quality of life and mood disorders is beneficial for the treatment of patients with RLS. Our study data appears to be related to the result that sleep disturbances and mental health disruptions might be associated with the disease severity among RLS patients.

Risk factors and clinical features associated with basal ganglia manganese deposition in patients with hereditary hemorrhagic telangiectasia.

BACKGROUND: T1-hyperintensity of the basal ganglia (BG) due to manganese deposition is a known radiologic finding in patients with hereditary hemorrhagic telangiectasia (HHT), but risk factors and associated clinical manifestations are unclear. This study conducted a quantitative analysis of the association of T1-hyperintensity in HHT patients with specific risk factors, signs, and symptoms. METHODS: Patients seen at our center between 2005 and 2020 with a definitive diagnosis of HHT who had an available non-contrast T1-weighted brain MRI were included. Hyperintensity was evaluated using oval regions of interest measurements. The BG: thalamus intensity ratio was used to quantitatively evaluate T1-hyperintensity. Patient laboratory values and clinical findings were collected from electronic medical records. Hyperintensity was analyzed for its association with laboratory values, and clinical findings. Variables were analyzed through regression analysis. RESULTS: A total of 239 patients were included in this study. On 1.5 T scanners, values that were significant on multivariable regression analysis were age (p < .001), hepatic AVMs (p < .001), iron deficiency anemia (p = .0021), and cirrhosis (p = .016). On 3 T scanners, values that were significant on multivariable analysis were hepatic AVMs (p = .0024) and cirrhosis (p = .0056). On 3 T scanners, hyperintensity was significantly associated with tremor (OR = 1.17, p = .033), restless leg syndrome (OR = 1.22, p = .0086), and memory problems (OR = 1.17, p = .046). CONCLUSIONS: BG hyperintensity due to manganese deposition is significantly associated with hepatic risk factors on 1.5 T and 3 T scanners and iron deficiency anemia on 1.5 T scanners. On 3 T scanners, T1-hyperintensity is associated with neuropsychiatric signs and symptoms, such as tremor, restless leg syndrome, and memory problems.

Restless leg syndrome in spinal cord injury: case report.

CASE DESCRIPTION: Restless leg syndrome (RLS) is a condition infrequently reported in spinal cord injury that causes an uncomfortable sensation in the legs and an urge to move them. We report a case involving a 63-year-old man with incomplete paraplegia with an onset of RLS four years post injury. FINDINGS: Based upon history, pramipexole was prescribed for the presumptive diagnosis of RLS, with good effect. Initial workup revealed an anemia (hemoglobin of 9.3 gram/deciliter (g/dl)) and iron deficiency (ferritin of 10 microgram/liter (µg/L)), necessitating further evaluation. CONCLUSION: Due to the complexities in diagnosing RLS in patients with SCI, it is important to be cognizant of symptoms and to consider this diagnosis to initiate the appropriate work-up for an etiology, of which iron deficiency anemia is common.

Neurologic Disorders in Women and Sleep.

Sleep disorders in women remain underrecognized and underdiagnosed mainly because of gender bias in researching and characterizing sleep disorders in women. Symptoms of common sleep disorders are frequently missed in the general female population and are expected to be further overlooked because of overlapping symptoms in women with neurologic disorders. Given the bidirectional relationship with sleep and neurologic disorders, it remains critical to be aware of the presentation and impact of sleep disorders in this patient population. This article reviews available data on sleep disorders in women with neurologic disorders and discusses their distinctive features.

Assessment of the Relationship between Non-motor features and Severity of Parkinson's Disease Patients in Bangladesh.

Parkinson's disease (PD) is second most common neurodegenerative disorder after Alzheimer's disease that may present with both motor and non-motor symptoms (NMSs). Many of the ignored NMSs may potentiate further deterioration of the patient's quality of life (QoL). But there is scarcity of data regarding NMSs of PD patients and their relationship with the disease severity in Bangladesh. This study was aimed to investigate the frequency of NMSs and assess their debatable impact on the severity of PD patients in Bangladesh. This cross-sectional type of observational study was conducted in neurology department of Dhaka Medical College Hospital, Bangladesh from January 2012 to June 2013 which recruited 60 eligible PD patients. The PD patients and disease severity was demonstrated by UK Parkinson's Disease Society Brain Bank criteria for idiopathic PD and the Hoehn and Yahr scale respectively. Whereas, NMSs were demonstrated by the self-structured questionnaire which had encountered 30 common symptoms of PD. The mean age of our study cohort was found 57.88±10.56 years with male female ration 2:1. According to the Hoehn and Yahr (H & Y) severity scale 38.3%, 38.3%, 20.1% and 3.3% patients had been suffering from stage ?, stage II, stage III and stage ?V Parkinson's disease respectively. Irrespective of the severity of the PD the frequency of NMSs was nocturia (66.7%), sadness or blues (65.0%), memory disturbance (61.7%), anxiety (58.3%), insomnia (56.7%), orthostatic hypotension (55.0%), erectile dysfunction (50.0%), urinary urgency (46.7%), anhedonia (45.0%), olfactory disturbance (38.3%), constipation (38.3%), hyper or hypo sexuality (31.7%) and restless leg syndrome (31.7%). However, after head-to-head NMSs analysis, daytime dribbling of saliva (p=0.024), urinary urgency (p=0.036), nocturia (p=0.001), weight loss (p=0.001), anhedonia (p=0.027), excessive daytime sleepiness (p=0.024), insomnia (p=0.007), vivid dream (p=0.024), REM behavior disorder (p=0.010), restless leg syndrome/ periodic leg movements (p=0.043) had significantly been reported higher among the stage II PD patients than that of stage I patients. Whereas fall (p=0.001), dysphagia or choking (p=0.002), constipation (p=0.003), fecal incontinence (p=0.033), excessive daytime sleepiness (p=0.033), anxiety (p=0.036) and anhedonia (p=0.044) were significantly more prevalent among the advanced stage (III) than stage (II) PD patients. Mean total NMS increased significantly with PD severity based on H and Y staging with a mean NMSQ-T (Non-Motor Symptoms Questionnaire Test) of 5.43 in stage 1, 9.22 in stage 2, 13.75 in stage 3 and 17.0 in stage 4 (p=0.0001). This study revealed that there was high frequency of NMSs among the PD patients and most common symptoms were nocturia, sadness, memory impairment, anxiety, insomnia, orthostatic hypotension, erectile dysfunction, anhedonia, urinary urgency and constipation. Finally, the more advanced disease as indicated by a higher H&Y stage was associated with significantly higher number of reported NMSs.

Restless Legs Syndrome and Restless Sleep Disorder in Children.

Restless legs syndrome (RLS) affects 2% of children presenting with symptoms of insomnia, restless sleep, decreased quality of life, and effects on cognition and behavior. The International RLS Study Group and the American Academy of Sleep Medicine have published guidelines for the diagnosis and treatment of RLS in children. Restless sleep disorder has been recently identified in children and presents with frequent movements during sleep and daytime symptoms with polysomnography findings of at least 5 large muscle movements at night. Treatment options for both disorders include iron supplementation, either oral or intravenous with improvement in nighttime and daytime symptoms.

A 9-year-old female with iron deficiency has severe periodic limb movements while taking mirtazapine for insomnia.

Mirtazapine is a Food and Drug Administration-approved atypical antidepressant used off-label for insomnia. Mirtazapine has been associated with movement disorders in adults. A 9-year-old female was seen in the sleep clinic for symptoms of insomnia, nocturnal awakenings, restless sleep, and growing pains. Mirtazapine was started prior to presentation for severe insomnia. A sleep study showed frequent repetitive leg movements prior to sleep onset as well as significant periodic limb movement disorder with a periodic limb movement index of 25.1/hour. The child was found to have a ferritin level of 23 ng/mL and an iron saturation of 10%. There were concerns that the presence of iron deficiency along with the use of mirtazapine may have contributed to the elevated periodic limb movement index. After starting iron therapy to treat the child's iron deficiency, mirtazapine was weaned off, with further clinical improvements in sleep quality reported. A follow-up sleep study showed a resolution of her periodic limb movement disorder with a periodic limb movement index of 1.4/hour. This is the first pediatric case to describe a sleep-related movement disorder associated with the use of mirtazapine and polysomnographic data to support resolution after discontinuation of mirtazapine along with iron therapy. CITATION: Hawkins M. A 9-year-old female with iron deficiency has severe periodic limb movements while taking mirtazapine for insomnia. J Clin Sleep Med. 2023;19(7):1369-1373.

Restless legs syndrome in DNAJC12 deficiency.

BACKGROUND: Restless legs syndrome (RLS) is characterized by an unpleasant or painful sensation generally localized to lower limbs and relieved by movement. Its pathogenesis is hypothesized to involve the dopaminergic system, also in the light of the response of RLS to ex adiuvantibus treatment with dopamine agonists. DNAJC12 deficiency is a recently identified inherited metabolic disease coupling hyperphenylalaninemia to deficient dopaminergic and serotoninergic neurotransmission, due to the combined impairment of the three aromatic amino acids' (i.e., phenylalanine, tyrosine, and tryptophan) hydroxylases. DNAJC12 deficiency was reported in 43 patients so far, presenting with wide spectrum of clinical symptoms. CASE PRESENTATION RESULTS: Here, we report RLS as a novel clinical manifestation of DNAJC12 deficiency, occurring in two adults while on treatment with L-dopa at longitudinal follow-up. The adjunct of low-dose pramipexole was effective in both patients to treat RLS. Besides, this treatment also allowed an improvement of dopaminergic homeostasis, as evidenced by clinical amelioration and stabilization of a peripheral short prolactin profile (a tool to indirectly evaluate dopaminergic homeostasis). DISCUSSION: Besides including RLS as a new treatable clinical manifestation of DNAJC12, these observations may suggest the opportunity of a selective screening for DNAJC12 deficiency in patients with idiopathic RLS.

Frequency, risk factors, and impacts on quality of life of the restless legs syndrome and side effects among antidepressant users in a tertiary hospital: an observational cross-sectional study.

Restless leg syndrome (RLS) is a common but underestimated sensorimotor disorder that significantly affects the quality of life (QoL) which can be induced by antidepressants. This study aims to investigate the frequency and potential risk factors of RLS and side effects in selective serotonin reuptake inhibitors/serotonin and noradrenaline reuptake inhibitors (SSRI/SNRI) users. This cross-sectional study included 198 outpatients who received SSRI/SNRI for 4-8 weeks. Clinical evaluation was performed using the International Restless Leg Syndrome Study Group rating scale for RLS, Udvalg for Kliniske Undersøgelser side effects rating scale, and a short form 36 (SF-36) questionnaire for QoL. The frequency of RLS was 25%. RLS significantly increased with smoking and habituality. Also, habituality increased neurologic side effects reporting. The use of antipsychotics and calcium channel blockers decreased reporting of autonomic side effects. QoL decreased with RLS, psychiatric, neurologic, autonomic, and other side effects in different domains of SF-36. These findings suggested that SSRI/SNRI use could be associated with a higher risk of RLS, especially in smokers. QoL could be influenced negatively by RLS and all side effects. However, further prospective studies are needed to confirm these associations in large samples.

Clonazepam for the management of sleep disorders.

BACKGROUND: The objectives of this review and meta-analysis of polysomnographic data are those to focus on the clinical use of clonazepam for the management of sleep disorders by re-analyzing clinical trials and randomized clinical trials which have been published in peer-reviewed journals. METHODS: A review of the literature including clinical trials and randomized controlled trials was performed in PubMed®, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement protocol. A random effects model meta-analysis was then carried out for the four more frequently reported polysomnographic measures: total sleep time, sleep latency, sleep efficiency, and periodic leg movement during sleep (PLMS) index. RESULTS: A total of 33 articles were retrieved and screened in full text, of which 18 met the criteria for review; among the latter, nine met the criteria for meta-analysis. The studies included in the review involved patients with insomnia, REM sleep behavior disorder, sleep bruxism, and restless leg syndrome or PLMS which reported, most often, an increase in total sleep time with clonazepam. A clear sleep-promoting effect of clonazepam was found also by meta-analysis. DISCUSSION AND CONCLUSIONS: Our results indicate that the pharmacological treatment of sleep disorders with clonazepam must always be personalized according to the type of patient, the risk of addiction and the concomitant presence of respiratory disorders are key factors to take into account. However, in light of the clinical evidence of the few studies in the literature on the different types of disorders, more studies on the use of clonazepam (also in association with first choice treatments) are definitely needed.