Background and Objectives A variety of neurologic disorders have been reported as presentations or complications of coronavirus disease 2019 (COVID-19) infection. The objective of this study was to determine their incidence dynamics and long-term functional outcome. Methods The Neuro-COVID Italy study was a multicenter, observational, cohort study with ambispective recruitment and prospective follow-up. Consecutive hospitalized patients presenting new neurologic disorders associated with COVID-19 infection (neuro-COVID), independently from respiratory severity, were systematically screened and actively recruited by neurology specialists in 38 centers in Italy and the Republic of San Marino. The primary outcomes were incidence of neuro-COVID cases during the first 70 weeks of the pandemic (March 2020–June 2021) and long-term functional outcome at 6 months, categorized as full recovery, mild symptoms, disabling symptoms, or death. Results Among 52,759 hospitalized patients with COVID-19, 1,865 patients presenting 2,881 new neurologic disorders associated with COVID-19 infection (neuro-COVID) were recruited. The incidence of neuro-COVID cases significantly declined over time, comparing the first 3 pandemic waves (8.4%, 95% CI 7.9–8.9; 5.0%, 95% CI 4.7–5.3; 3.3%, 95% CI 3.0–3.6, respectively; p = 0.027). The most frequent neurologic disorders were acute encephalopathy (25.2%), hyposmia-hypogeusia (20.2%), acute ischemic stroke (18.4%), and cognitive impairment (13.7%). The onset of neurologic disorders was more common in the prodromic phase (44.3%) or during the acute respiratory illness (40.9%), except for cognitive impairment whose onset prevailed during recovery (48.4%). A good functional outcome was achieved by most patients with neuro-COVID (64.6%) during follow-up (median 6.7 months), and the proportion of good outcome increased throughout the study period (r = 0.29, 95% CI 0.05–0.50; p = 0.019). Mild residual symptoms were frequently reported (28.1%) while disabling symptoms were common only in stroke survivors (47.6%). Discussion Incidence of COVID-associated neurologic disorders decreased during the prevaccination phase of the pandemic. Long-term functional outcome was favorable in most neuro-COVID disorders, although mild symptoms commonly lasted more than 6 months after infection.

Introduction: By the end of 2019, severe acute respiratory syndrome coronavirus 2 rapidly spread all over the world impacting mental health and sleep habits. Insomnia, impaired sleep quality, and circadian rhythm alterations were all observed during the pandemic, especially among healthcare workers and in patients with acute and post-acute COVID-19. Sleep disruption may induce a pro-inflammatory state associated with an impairment of immune system function.Objective: We investigated the relationship between sleep alterations, psychological disorders, and inflammatory blood biomarkers in patients with post-acute COVID-19.Methods: We enrolled 47 subjects diagnosed with COVID-19 pneumonia at Santa Maria della Misericordia University Hospital (Udine, Italy) between March and May 2020. Selected patients were evaluated at 2 months (T1) and 10 months (T2) after discharge. Each time, we collected clinical interviews, neurological examinations, and self-administered questionnaires to assess sleep and life quality, anxiety, depression, and post-traumatic stress disorder. Blood biomarkers of endothelial activation, neuroinflammation, and inflammatory cytokines were also measured at each follow-up. Collected variables were analyzed using comparisons between groups and linear regression models.Results: Prevalence of insomnia increased from 10.6% up to 27.3% after COVID-19. Poor sleep quality was found in 41.5% of patients at both study visits. At T1 follow-up, poor sleepers showed higher levels of neurofilament light chain, vascular cell adhesion molecule 1, and interleukin 10; no significant associations were found between sleep quality and psychological disorders. At T2 follow-up, lower sleep quality was associated with higher levels of vascular cell adhesion molecule 1 and interleukin 8, but also with higher scores for anxiety, depression, and post-traumatic stress disorder.Conclusion: Our results suggest an association of poor sleep quality with both psychological disorders and neuroinflammation, although at different times, in previously hospitalized patients with moderate-to-critical COVID-19.

Introduction: Migraine and sleep share a complex and unclear relationship. Poor sleep may trigger migraine attacks; migraine, in turn, is frequently associated with sleep disorders. Few previous studies used questionnaires to assess sleep changes in patients who were treated with migraine-preventive medications (MPMs). More extensive polysomnography (PSG)-based studies for this purpose were not available.Objective: To investigate possible sleep changes in patients with migraine treated with erenumab, using validated sleep questionnaires and home-PSG.Methods: This observational, prospective, open-label pilot study was conducted at the Clinical Neurology Unit Headache Center of Udine University Hospital from 2020 to 2021. Patients were treated with erenumab as monotherapy or add-on treatment for migraine prevention. Sleep changes were evaluated with questionnaires and polysomnographic recordings at baseline, after 3 and 12 months of treatment. Erenumab efficacy and safety in migraine prophylaxis were also investigated.Results: Twenty-nine patients completed 3 months of follow-up, whereas 15 patients completed 12 months. We found a weak trend of improvement in daytime somnolence after 3 months of treatment, with stronger results after 12 months (median Epworth Sleepiness Scale (ESS) score from 6.0 to 4.0, p = 0.015); a significant improvement in subjective sleep quality (median Pittsburgh Sleep Quality Index (PSQI) total score from 7 to 5; p = 0.001) was also observed. Home-PSG showed a significant increase in objective sleep efficiency (SE), both after 3 (from 88.1 to 91.0, p = 0.006) and 12 months (from 87.1 to 91.0, p = 0.006) of treatment. In addition, our data confirmed erenumab effectiveness and safety in migraine prevention.Conclusion: Our study demonstrated an improvement in both subjective and objective sleep quality in patients treated with a migraine-preventive therapy. Erenumab, in particular, does not cross the blood-brain barrier (BBB), thus a direct effect on sleep is unlikely. Future studies are needed to better understand the mutual influence between migraine and sleep disorders.

In the context of neurodegenerative disorders, cognitive decline is frequently reported in older population. Recently, numerous metabolic pathways have been implicated in neurodegeneration, including signaling disruption of insulin and other glucose-regulating hormones. In fact, Alzheimer’s disease has now been considered as “type-3 diabetes”. In this review, we tried to clarify the role of sleep impairment as the third major player in the complex relationship between metabolic and neurodegenerative diseases. Altered sleep may trigger or perpetuate these vicious mechanisms, leading to the development of both dementia and type 2 diabetes mellitus. Finally, we analyzed these reciprocal interactions considering the emerging role of the gut microbiota in modulating the same processes. Conditions of dysbiosis have been linked to circadian rhythm disruption, metabolic alterations, and release of neurotoxic products, all contributing to neurodegeneration. In a future prospective, gut microbiota could provide a major contribution in explaining the tangled relationship between sleep disorders, dementia and diabetes.

Restless legs syndrome/Willis-Ekbom disease (RLS/WED) is a sleep-related sensory-motor disorder associated with poor sleep quality and impaired daily functioning. In patients affected by chronic RLS/WED, a pharmacological therapy is recommended. International guidelines suggest to start the treatment with a α2δ calcium channel ligand in most cases, unless contraindicated. The present review is based on an extensive Internet and PubMed search from 1986 to 2024. Our purpose is to describe the absorption, distribution, metabolism, and toxicology (ADMET) of the α2δ ligands, with common consideration for the therapeutic class, specificities of different compounds, efficacy, and safety in relation to other treatment options. α2δ ligands are quite similar in their ADMET profiles, sharing most of the pharmacokinetics and potential adverse effects. However, we highlight the linear kinetic of gabapentin enacarbil and pregabalin, differently from gabapentin. α2δ ligands are safe and effective for the treatment of RLS/WED. Additional benefits can be obtained in comorbid insomnia, chronic pain syndromes, history of impulse control disorder, and comorbid anxiety. The use of α2δ ligands is associated with poor risk of augmentation. We still need new long-term safe and effective treatments, which could be developed along with our knowledge of RLS/WED pathophysiology.