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. 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 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.

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.

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.

Sleep-Related Breathing Disorders in Multiple Sclerosis: Prevalence, Features and Associated Factors.

Background: Multiple sclerosis (MS) represents a risk factor for sleep disorders, but there are conflicting results about the prevalence and severity of sleep-related breathing disorders (SRBD) in MS. Most available data come from self-administered questionnaires. Objective: To conduct a polysomnographic study in MS focused on SRBD, compared to a group of healthy controls (HC), also considering the neuroimaging findings. To evaluate the impact of SRBD on vigilance, fatigue and depression in MS. Methods: In this cross-sectional, observational, instrumental study, 67 MS patients (men/women: 20/47; mean age: 50.6±8.2 years) underwent PSG and maintenance of wakefulness test. Findings were compared to 67 age-, sex-, BMI-matched HC, by using parametric (Student's t-test) and nonparametric statistics (chi-squared test). A subgroup analysis was then performed, evaluating the influence of brainstem (mesencephalic, pontine and medullary) lesions at neuroimaging on instrumental and clinical data: MS patients with at least one brainstem lesion vs MS patients without vs HC. Results: The frequency of SRBD was comparable in MS patients and HC. No MS patient had a central apnea index ≥2/h. The respiratory disturbance index (RDI) did not correlate to clinical parameters such as fatigue and depression. Patients with MS were drowsier than HC (47% vs 26%, p = 0.019) and showed a worse sleep pattern, in terms of duration, efficiency and architecture. Conclusion: Our study does not provide evidence of an association between MS-specific symptoms such as fatigue, sleepiness, depression and central or obstructive apneas, even in the presence of brainstem lesions.

Leg movement activity during sleep in multiple sclerosis with and without restless legs syndrome.

STUDY OBJECTIVES: To carry out an analysis of leg movement activity during sleep in a polysomnography dataset of patients with multiple sclerosis (MS) in comparison to idiopathic restless legs syndrome (iRLS) and healthy controls. METHODS: In this cross-sectional, observational, instrumental study, 57 patients (males/females: 11/46; mean age 46.2 ± 10.2 years) with a diagnosis of MS underwent a telephone interview assessing the 5 standard diagnostic criteria for RLS and polysomnography. Sleep architecture and leg movement activity during sleep were subsequently compared: 1) 40 patients with MS without RLS (MS-RLS) vs 28 healthy controls; 2) 17 patients with MS with RLS (MS+RLS) vs 35 patients with iRLS; 3) MS+RLS vs MS-RLS. RESULTS: MS-RLS and MS+RLS presented increased sleep latency, percentage of sleep stage N1, and reduced total sleep time compared to healthy controls and iRLS, respectively. The periodic limb movements during sleep (PLMS) index was higher in MS-RLS than in healthy controls (P = .035) and lower in MS+RLS compared to iRLS (P = .024). PLMS in MS+RLS were less periodic, less often bilateral, and with shorter single movements compared to the typical PLMS in iRLS. CONCLUSIONS: MS is a risk factor for RLS, PLMS, and for a lower sleep quality in comparison to healthy patients. PLMS in MS+RLS are fewer and shorter if compared to iRLS. Our results suggest a dissociation between motor (PLMS) and sensory symptoms (RLS sensory component) in RLS secondary to MS, with possible treatment implications. CITATION: Ferri R, Sparasci D, Castelnovo A, et al. Leg movement activity during sleep in multiple sclerosis with and without restless legs syndrome. J Clin Sleep Med. 2022;18(1):11-20.

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.

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.

Restless legs syndrome and periodic limb movements in 86 patients with multiple sclerosis.

STUDY OBJECTIVES: To assess the frequency of restless legs syndrome (RLS), periodic limb movements during sleep (PLMS), and their overlap in a large sample of patients with multiple sclerosis (MS). To compare clinical and paraclinical findings among four subgroups of patients: RLS-/PLMS- (patients without RLS and PLMS), RLS+/PLMS- (patients with RLS and without PLMS), RLS-/PLMS (patients without RLS and with PLMS), and RLS+/PLMS+ (patients with both RLS and PLMS). METHODS: In this cross-sectional, observational, instrumental study, 86 patients (M/F: 27/59; mean age 48.0 ± 10.8 years) with a diagnosis of MS underwent a telephone interview assessing the five standard diagnostic criteria for RLS. Seventy-six participants underwent polysomnography (PSG) and maintenance of wakefulness test (MWT). Instrumental and clinical findings were subsequently statistically compared to investigate their association with RLS and PLMS index (PLMSI). RESULTS: RLS and PLMS (PLMSI ≥15/h) frequency in patients with MS were of 31.4% and 31.6%, respectively. Among patients with RLS, 37.5% had a PLMSI of at least 15/h. RLS-/PLMS+ group showed higher wake after sleep onset (p = 0.01), stage shifts per hour (p = 0.03), increased stage N1 (p = 0.03), and reduction in stage N3 (p = 0.01) compared to RLS-/PLMS-. RLS had no influence on clinical and PSG parameters (p = 0.45). CONCLUSIONS: RLS is highly frequent in patients with MS. The frequency of PLMS is comparable to the general population. The low percentage of patients with RLS having a high PLMSI, together with the absence of correlation between RLS and female gender and older age, supports the existence of a distinct symptomatic form of RLS in MS.

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.