Fatigue, sleepiness and depression in multiple sclerosis: defining the overlaps for a better phenotyping.

BACKGROUND AND OBJECTIVES To define the boundaries and the overlaps between fatigue, sleepiness and depression in patients with multiple sclerosis (MS) by using different tools for each dimension, including instrumental sleep analysis. METHODS In this cross-sectional, observational study, 71 MS patients (males/females: 20/51; mean age: 48.9 ± 10.5 years) filled in clinical questionnaires and performed polysomnography followed by maintenance of wakefulness test (MWT). Frequency and reciprocal overlap of sleepiness, fatigue and depression in MS were expressed by Eulero-Venn diagrams; standard multiple regression was used to assess the ability of symptoms to predict each other. RESULTS There was a high percentage of fatigued (70%), somnolent (45%) and depressed (27%) patients. Fatigue had the strongest overlap and correlated with both depression (beta: 0.52, p < 0.001) and sleepiness (beta: 0.74, p < 0.001). Somnolence and depression were nearly always accompanied by fatigue and were well differentiated from each other by MWT. Four MS subgroups were identified that had: (1) fatigue only; (2) fatigue and sleepiness (3) fatigue and depression; (4) fatigue, sleepiness and depression. DISCUSSION The subjective and objective tools are not able to clearly distinguish fatigue from sleepiness and depression, while only a test of vigilance can be helpful in separating somnolence and depression from each other

Prostate Cancer and Sleep Disorders: A Systematic Review.

Prostate cancer (PCa) treatment involves multiple strategies depending on the disease's stage. Androgen deprivation therapy (ADT) remains the gold standard for advanced and metastatic stages. Sleep quality has been suggested as being additionally influenced also by local radiotherapy, prostatectomy and androgen-receptor (AR)-targeted agents. We performed a systematic review exploring the landscape of studies published between 1 January 1990 and 31 July 2021, investigating sleep disturbances in PCa patients receiving active treatments, including the influence of hormonal therapy on sleep quality as a factor affecting their quality of life. Out of 45 articles identified, 16 studies were selected, which recruited patients with PCa, undergoing active treatment in either a prospective longitudinal or cross-sectional study. Development of sleep disorders or changes in sleep quality were reported in 14 out of 16 trials included. Only five trials included objective measurements such as actigraphy, mostly at one time point and without a baseline assessment. Limitations to be addressed are the small number of existing trials, lack of randomized trials and heterogeneity of methodologies used. This systematic review outlines the lack of prospective trials investigating sleep disorders, with a rigorous methodology, in homogeneous cohorts of PCa patients. Future trials are needed to clarify the prevalence and impact of this side effect of PCa treatments

Prostate Cancer and Sleep Disorders: A Systematic Review

Prostate cancer (PCa) treatment involves multiple strategies depending on the disease&rsquo;s stage. Androgen deprivation therapy (ADT) remains the gold standard for advanced and metastatic stages. Sleep quality has been suggested as being additionally influenced also by local radiotherapy, prostatectomy and androgen-receptor (AR)-targeted agents. We performed a systematic review exploring the landscape of studies published between 1 January 1990 and 31 July 2021, investigating sleep disturbances in PCa patients receiving active treatments, including the influence of hormonal therapy on sleep quality as a factor affecting their quality of life. Out of 45 articles identified, 16 studies were selected, which recruited patients with PCa, undergoing active treatment in either a prospective longitudinal or cross-sectional study. Development of sleep disorders or changes in sleep quality were reported in 14 out of 16 trials included. Only five trials included objective measurements such as actigraphy, mostly at one time point and without a baseline assessment. Limitations to be addressed are the small number of existing trials, lack of randomized trials and heterogeneity of methodologies used. This systematic review outlines the lack of prospective trials investigating sleep disorders, with a rigorous methodology, in homogeneous cohorts of PCa patients. Future trials are needed to clarify the prevalence and impact of this side effect of PCa treatments

Correction to: Severe restless legs syndrome in a family with Alport syndrome.

BACKGROUND: Restless legs syndrome (RLS) is a common sleep-related movement disorder characterized by an urge to move the legs during inactivity, especially at evening-night. RLS is highly prevalent in patients with kidney failure and have an impact on quality of life, mood, sleep quality and overall on compliance to the dialysis. Alport syndrome (AS) is a rare inherited disease, predominantly X-linked, secondary to mutations in genes encoding α3, α4 or α5 chains of type IV collagen, and characterized by hematuria, chronic kidney disease, neurosensory deafness, and lenticonus. CASE PRESENTATION: Here we describe a family with a combination of X-linked AS and severe RLS accompanied by periodic limb movements during sleep (PLMS). In the first patient we identified, RLS was complicated by a paradoxical response to dopamine agonists named “augmentation”, leading to sleep disruption, hallucinations and five peritoneal perforations during the peritoneal dialysis due to the difficulty to rest still. Therapeutic adjustments and renal transplantation improved RLS and PLMS. In two brothers, severe RLS prevented a compliance with hemodialysis. Female family members carrying the mutation were also affected by RLS, while those without the mutations were RLS-free. CONCLUSIONS: RLS has not been reported earlier in association with AS, but the peculiar combinations observed in this family will stimulate further clinical studies and motivate nephrologists to seek for RLS symptoms and sleep disturbances in AS patients

Relationship between cognitive disturbances and sleep disorders in multiple sclerosis is modulated by psychiatric symptoms.

BACKGROUND Multiple sclerosis (MS) patients with cognitive impairment (CI) frequently suffer from sleep disturbances and emotional symptoms. The aim of this study was to investigate the relationship between CI and sleep disturbances and the role of anxiety and depression on this relationship in MS patients. METHODS Prospective cross-sectional study including 80 MS patients that underwent neurologic, cognitive, psychiatric assessment, and polysomnographic registration. Partial correlations analysis adjusted by demographic and clinical variables were used to investigate associations between cognitive and sleep measures. Moderator role effect of psychiatric symptoms was also explored with linear models. RESULTS Thirty-six MS patients had CI. In all patients, worse performances at global, memory and attention cognitive domains were correlated with reduced sleep efficacy and longer periods of nocturnal wake (NW), while poor attention performances were associated with reduced REM-sleep (r = 0.26, p = 0.022). Memory performances were also negatively correlated with anxiety (r = -0.27, p = 0.015). The relationship between NW and memory performances was moderated by trait anxiety (p < 0.001). CONCLUSIONS Our findings suggest that low sleep efficiency, NW, and reduced REM-sleep might affect cognitive abilities in MS. Higher trait anxiety appeared to impact on the relationship between increased NW and poor memory performances. Treatment of sleep and psychiatric disturbances may contribute to mitigating cognitive disorders in MS

Contribution of sleep disturbances to fatigue in multiple sclerosis: a prospective study using clinical and polysomnographic parameters

Background and purpose: Fatigue is amongst the most frequent and disabling symptoms of multiple sclerosis and a close relation between fatigue and sleep quality has been hypothesized. In this study the contribution of sleep disturbances measured by clinical and polysomnographic parameters to fatigue in multiple sclerosis was investigated. Methods: This was a prospective instrumental study performed at the Neurocenter of Southern Switzerland. Demographic data and clinical characteristics including fatigue (as measured by the modified fatigue impact scale [MFIS]), neurological disability, psychiatric symptoms, medications and sleep-related variables were collected at baseline visit and by a home full-night polysomnography. The associations between sleep-related variables and the MFIS were tested using partial correlations adjusted by demographic and sleep-unrelated clinical factors. Results: Seventy-six patients were included in the study, of whom 53 (69.7%) had an MFIS ≥38 points (median 49.5, interquartile range 31.0– 62.0). MFIS scores were positively associated with age, neurological disability, symptoms of depression and anxiety, and use of benzodiazepines and selective serotonin reuptake inhibitors. When adjusting for these variables, the presence of restless legs syndrome (RLS) (r = 0.37, p = 0.005) and periodic leg movements index (r = −0.33, p = 0.014) were associated with MFIS. Excessive daytime sleepiness, total sleep time, sleep efficiency, respiratory disturbances, and percentage of time spent in the different sleep stages (N1, N2, N3 and rapid eye movement) were not associated with fatigue. Conclusions: Multiple sclerosis patients with a diagnosis of RLS had significantly higher global fatigue scores compared to those without RLS. Future studies should investigate whether medical treatment of RLS can ameliorate fatigue

Neuropathies related to hepatitis E virus infection: A prospective, matched case–control study

Background: Acute hepatitis E virus (HEV) infection has recently emerged as a potential trigger for acute dysimmune neuropathies, but prospective controlled studies are lacking.AimsTo compare the frequency of concomitant acute HEV infection in patients with neuralgic amyotrophy (NA), Guillain–Barré syndrome (GBS), and Bell's palsy with a matched control population. Methods: Swiss multicenter, prospective, observational, matched case–control study over 3 years (September 2019–October 2022). Neurological cases with NA, GBS, or Bell's palsy were recruited within 1 month of disease onset. Healthy controls were matched for age, sex, geographical location, and timing of blood collection. Diagnostic criteria for acute hepatitis E were reactive serum anti‐HEV IgM and IgG assays (ELISA test) and/or HEV RNA detection in serum by real‐time polymerase chain reaction (RT‐PCR). RT‐PCR was performed on sera to confirm IgM positivity. Results: We included 180 patients (59 GBS, 51 NA, 70 Bell's palsy cases) and corresponding matched controls (blood donors) with median age 51 years for both groups and equal gender distribution. Six IgM+ cases were detected in the NA, two in the GBS, and none in the Bell's palsy group. Two controls were anti‐HEV IgM‐positive. At disease onset, most cases with acute HEV infection had increased liver enzymes. A moderate association (p = 0.027, Fisher's exact test; Cramér's V = −0.25) was observed only between acute HEV infection and NA. Conclusion: This prospective observational study suggests an association between concomitant acute HEV infection and NA, but not with GBS or Bell's palsy

Effects of Circadian Phase Tailored Light Therapy on Sleep, Mood, and Cognition in Alzheimer's Disease: Preliminary Findings in a Pivotal Study

It is shown that the circadian system is affected in patients with Alzheimer's disease (AD) even at an early stage of the disease and that such dysfunction may be detrimental to sleep, mood, and cognitive functioning. Light is a strong central modulator of the circadian rhythms and is potentially beneficial to mood and cognitive functioning via a direct effect or indirectly via its modulating effects on circadian rhythms. This study focuses on tracking the effect of light therapy on sleep quality, mood, and cognition in AD of mild/moderate severity. We performed a single-blind randomized controlled trial to investigate the effects of a light therapy treatment tailored to the individual circadian phase as measured by dim light melatonin onset (DLMO). Such a treatment induced an objective circadian phase shift consistent with the melatonin phase response curve to light exposure, led to a shortening of the phase angle DLMO-falling asleep time, and was associated with an improvement in subjective sleep quality and cognitive performance

Neuropathies related to hepatitis E virus infection: A prospective, matched case-control study.

BACKGROUND Acute hepatitis E virus (HEV) infection recently emerged as a potential trigger for acute dysimmune neuropathies, but prospective controlled studies are lacking. AIMS To compare the frequency of concomitant acute HEV infection in patients with neuralgic amyotrophy (NA), Guillain-Barré syndrome (GBS), and Bell's palsy with a matched control population. METHODS Swiss multicentre, prospective, observational matched case-control study over 3 years (09.2019-10.2022). Neurological cases with NA, GBS or Bell's palsy were recruited within 1 months from disease onset. Healthy controls were matched for age, sex, geographical location, and timing of blood collection. Diagnostic criteria for acute hepatitis E were reactive serum anti-HEV IgM and IgG assays (ELISA test) and/or HEV RNA detection in serum by Real-time-PCR (RT-PCR). RT-PCR was performed on sera to confirm IgM positivity. RESULTS We included 180 patients (59 GBS, 51 NA, and 70 Bell's palsy cases) and corresponding matched controls (blood donors), with median age of 51 years for both groups and equal gender distribution. Six IgM+ cases were detected in the NA, two in the GBS, and none in the Bell's palsy group. Two controls were anti-HEV IgM positive. At disease onset, most cases with acute HEV infection had increased liver enzymes. A moderate association (p=0.027; Cramér's V = -0.25, Fisher exact test) was observed only between acute HEV infection and NA. CONCLUSION This prospective observational study suggests an association between concomitant acute HEV infection and NA, but not with GBS or Bell's palsy