Critically appraised topic on Rapid Eye Movement Behavior Disorder: From protein misfolding processes to clinical pathophysiology and conversion to neurodegenerative disorders

Background: REM Behavior Disorder (RBD) is considered one of most powerful prodromal condition in different neurodegenerative disorders, mainly alpha-synucleinopathies. A large amount of research recently explored this relationship. Objective and Design: The present critically appraised review undertakes this topic, from the perspective of the pathogenetic interplay between clinical manifestations in RBD patients and the misfolding processes that characterize neurodegeneration. In particular, evidence in favor and against the role of RBD as a biomarker of neurodegeneration is discussed. Results and Conclusion: The selected papers were functional to structure the review into three main sections: 1) Protein misfolding in neurodegenerative disorders with focus on alpha-synuclein; 2) Clinical features, diagnosis, and pathophysiology of RBD; 3) RBD as a clinical biomarker of protein misfolding. Data herein highlights the current knowledge and the areas of uncertainties in the relationship between RBD and neurodegenerative disorders; we went through preclinical, prodromal and clinical stages of neurodegenerative processes as a useful reference for clinicians involved in brain pathological aging and future research in this field

A Case Report of Pulsed Radiofrequency Plus Suboccipital Injection of the Greater Occipital Nerve: An Easier Target for Treatment of Cluster Headache

Introduction: In cluster headache, the efficacy of suboccipital steroid injection is notable within a few days, although few data are available about the duration of efficacy. A combination treatment, consisting of suboccipital steroid injection plus pulsed radiofrequency, could potentially lead to long-term benefit. Evidence about pulsed radiofrequency of the greater occipital nerve is lacking. Patients and Methods: We retrospectively describe a series of four cluster headache patients treated with suboccipital steroid injection plus pulsed radiofrequency of the greater occipital nerve. Results: All patients achieved a 50% reduction in attack frequency in the 7 days after the first treatment. Moreover, a long pain-free remission period up to 15 months was noted. Conclusion: Suboccipital steroid injection plus pulsed radiofrequency of the greater occipital nerve might have both acute and prophylactic effects in cluster headache. The greater occipital nerve is more accessible to pulsed radiofrequency than other targets

Erenumab Impact on Sleep Assessed With Questionnaires and Home-Polysomnography in Patients With Migraine: The ERESON Study

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

Restless legs syndrome in internal medicine

Restless legs syndrome/Willis-Ekbom Disease (RLS/WED) is a common but still underdiagnosed neurological disorder. RLS/WED might impair nocturnal rest causing decreased alertness, depression, reduced job performance and poor quality of life. RLS/WED can occur as an isolated disease, mostly at a young age, or can be associated with comorbidities such as cardiovascular disease, diabetes, renal failure, arterial hypertension and peripheral neuropathy. The literature also offers some evidence of an association with gastrointestinal, rheumatological, pneumological, and neoplastic disorders. It is important to be aware of these associations in order to promptly recognize RLS/WED and also to think about an underlying medical condition when a patient reports symptoms of RLS/WED

Clinical and neurophysiological characterization of muscular weakness in severe COVID-19

Objective: To report clinical and electroneuromyographic (ENMG) characteristics of patients affected by severe COVID-19 infection, evaluated for muscular weakness. Materials and methods: ENMGs performed for evaluation of diffuse weakness in patients who could not be discharged from semi-intensive care COVID unit because of difficulties in ventilation weaning were reviewed. Patients with severe COVID-19 infection who had undergone endotracheal intubation and able to co-operate were considered. ENMG protocol was focused on neurophysiological items that excluded or confirmed critical illness polyneuropathy (CIP), myopathy (CIM), or polyneuromyopathy (CIPM). Standardized clinical evaluation was performed using Medical Research Council (MRC) sum score. Results: Eight patients were included in the study. All presented known risk factors for intensive care unit-acquired weakness (ICU-AW), and none of them had history of underlying neuromuscular disorders. ENMG findings were normal in two patients, while only two patients had an altered MRC sum score (< 48). Neuromuscular involvement was diagnosed in 6/8 patients (75%): 2 had CIP, 1 had possible CIM, 1 had CIPM, while 1 patient, with clinically evident weakness but equivocal ENMG findings, was classified as ICU-AW. Finally, 1 patient was diagnosed with acute demyelinating neuropathy. Patients with neuromuscular involvement were those with longer intubation duration and higher levels of IL-6 at admission. Conclusion: Neuromuscular complications are frequent in severe COVID-19 and cannot be excluded by MRC sum scores above 48. Standardized ENMG is helpful in guiding diagnosis when clinical evaluation is not reliable or possible. Elevated IL-6 at admission may be a predictor biomarker of ICU-AW in COVID-19

Hyposmia and Dysgeusia in COVID-19: Indication to Swab Test and Clue of CNS Involvement

OBJECTIVE: To evaluate the prevalence of hyposmia and dysgeusia in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and their temporal relationship with the onset of other symptoms. METHODS: We performed a retrospective analysis of patients admitted during the month of March 2020 to the nonintensive COVID unit of Udine University Hospital on the basis of a positive swab test and/or of clinical-radiologic signs of SARS-CoV-2 infection. Patients were interviewed with a standardized questionnaire. Clinical and laboratory data were collected. Data were analyzed with descriptive statistics, and results expressed as point estimates and 95% confidence intervals (CIs). RESULTS: Of 141 patients admitted, 93 were interviewed. Hyposmia and dysgeusia were present in 58 cases (62.4%). In 22.4% of them, olfactory and gustatory impairment clearly preceded systemic symptoms. The presence of active smoking was very limited in both groups: 8.6% in hyposmic vs 2.9% in normosmic patients (odds ratio 3.2; 95% CI 0.3–28.6). Moreover, total leukocytes and neutrophils count were respectively 23% (effect estimate 1.23; 95% CI 1.06–1.42) and 29% (effect estimate 1.29; 95% CI 1.07–1.54) lower in the hyposmic cohort. No difference was found for other inflammatory biomarkers. CONCLUSIONS: Hyposmia and dysgeusia are common in SARS-CoV-2 infection and can precede systemic symptoms. They should be actively searched and prompt close monitoring and isolation until infection is confirmed or disproven. The lower number of total leukocytes and neutrophils in hyposmic patients might indicate an early-phase virus-induced cytopenia

Circulating levels of soluble adhesion molecules in patients with ANCA-associated vasculitis

BACKGROUND: During inflammation, activated vascular endothelial cells and other cell types express various adhesion molecules, which facilitate the binding of circulating leukocytes and their extravasation in surrounding tissue (i.e. renal tissue). The serum concentration of circulating soluble adhesion molecules is supposed to reflect the degree of this activation. OBJECTIVE: In the first part of the study, we determined if the serum levels of the soluble intercellular adhesion molecule (sICAM)-1 and the soluble endothelial cell-leukocyte adhesion molecule (sELAM)-1, in patients affected by microscopic polyangiitis (MPA), associated with myeloperoxidase (MPO)-anti-neutrophil cytoplasmic antibodies (ANCA), were related to the active and the inactive vasculitis phase. In the second part of the study, we examined the changes in circulating sICAM-1 and sELAM-1 levels and the clinical outcome of renal function in these patients. METHODS: We examined 20 MPO-ANCA-positive MPA patients in an acute phase and in a remission phase, after 6 months of treatment, and 50 subjects as controls, 30 with autosomal dominant polycystic kidney disease (ADPKD) in stable chronic renal failure (CRF) and 20 healthy volunteers (HS) with normal renal function. RESULTS: Regarding serum creatinine (Cr) concentration, no significant differences were found comparing active and inactive phases in the MPA group and the CRF group. Mean serum adhesion molecule levels in the MPA group were higher in the active phase compared to the inactive phase and to the CRF and HS groups. In addition, considering the outcome of serum Cr concentrations in the MPA group, the serum adhesion molecule levels were higher and decreased more slowly in patients with final high serum Cr concentrations than in patients with final normal serum Cr concentrations. CONCLUSION: Our data suggest that in MPO-ANCA-positive MPA patients, higher sICAM-1 and sELAM-1 levels during the active phase and their slower decline during the treatment period, could be a prognostic risk factor for CRF development