Non-demyelinating disorders mimicking and misdiagnosed as NMOSD: a literature review.

BACKGROUND: Differentiating neuromyelitis optica spectrum disorder (NMOSD) from its mimics is crucial to avoid misdiagnosis, especially in the absence of aquaporin-4-IgG. While multiple sclerosis (MS) and myelin oligodendrocyte glycoprotein-IgG associated disease (MOGAD) represent major and well-defined differential diagnoses, non-demyelinating NMOSD mimics remain poorly characterized. METHODS: We conducted a systematic review on PubMed/MEDLINE to identify reports of patients with non-demyelinating disorders that mimicked or were misdiagnosed as NMOSD. Three novel cases seen at the authors' institutions were also included. The characteristics of NMOSD mimics were analyzed and red flags associated with misdiagnosis identified. RESULTS: A total of 68 patients were included; 35 (52%) were female. Median age at symptoms onset was 44 (range, 1-78) years. Fifty-six (82%) patients did not fulfil the 2015 NMOSD diagnostic criteria. The clinical syndromes misinterpreted for NMOSD were myelopathy (41%), myelopathy + optic neuropathy (41%), optic neuropathy (6%), or other (12%). Alternative etiologies included genetic/metabolic disorders, neoplasms, infections, vascular disorders, spondylosis, and other immune-mediated disorders. Common red flags associated with misdiagnosis were lack of cerebrospinal fluid (CSF) pleocytosis (57%), lack of response to immunotherapy (55%), progressive disease course (54%), and lack of magnetic resonance imaging gadolinium enhancement (31%). Aquaporin-4-IgG positivity was detected in five patients by enzyme-linked immunosorbent assay (n = 2), cell-based assay (n = 2: serum, 1; CSF, 1), and non-specified assay (n = 1). CONCLUSIONS: The spectrum of NMOSD mimics is broad. Misdiagnosis frequently results from incorrect application of diagnostic criteria, in patients with multiple identifiable red flags. False aquaporin-4-IgG positivity, generally from nonspecific testing assays, may rarely contribute to misdiagnosis.

Why we need to pursue both universal and targeted prevention to reduce the incidence of affective and psychotic disorders: Systematic review and meta-analysis.

The effectiveness of universal preventive approaches in reducing the incidence of affective/psychotic disorders is unclear. We therefore aimed to synthesise the available evidence from randomised controlled trials. For studies reporting change in prevalence, we simulated all possible scenarios for the proportion of individuals with the disorder at baseline and at follow-up to exclude them. We then combined these data with studies directly measuring incidence and conducted random effects meta-analysis with relative risk (RR) to estimate the incidence in the intervention group compared to the control group. Eighteen studies (k=21 samples) were included investigating the universal prevention of depression in 66,625 individuals. No studies were available investigating universal prevention on the incidence of bipolar/psychotic disorders. 63 % of simulated scenarios showed a significant preventive effect on reducing the incidence of depression (k=9 - 19, RR=0.75-0.94, 95 %CIs=0.55-0.87,0.93-1.15, p=0.007-0.246) but did not survive sensitivity analyses. There is some limited evidence for the effectiveness of universal interventions for reducing the incidence of depression but not for bipolar/psychotic disorders.

The lived experience of mental disorders in adolescents: a bottom-up review co-designed, co-conducted and co-written by experts by experience and academics.

We provide here the first bottom-up review of the lived experience of mental disorders in adolescents co-designed, co-conducted and co-written by experts by experience and academics. We screened first-person accounts within and outside the medical field, and discussed them in collaborative workshops involving numerous experts by experience - representing different genders, ethnic and cultural backgrounds, and continents - and their family members and carers. Subsequently, the material was enriched by phenomenologically informed perspectives and shared with all collaborators. The inner subjective experience of adolescents is described for mood disorders, psychotic disorders, attention-deficit/hyperactivity disorder, autism spectrum disorders, anxiety disorders, eating disorders, externalizing disorders, and self-harm behaviors. The recollection of individuals' past histories also indexes the prodromal (often transdiagnostic) features predating the psychiatric diagnosis. The experience of adolescents with mental disorders in the wider society is described with respect to their family, their school and peers, and the social and cultural context. Furthermore, their lived experience of mental health care is described with respect to receiving a diagnosis of mental disorder, accessing mental health support, receiving psychopharmacological treatment, receiving psychotherapy, experiencing peer support and mental health activism, and achieving recovery. These findings can impact clinical practice, research, and the whole society. We hope that this co-designed, co-conducted and co-written journey can help us maintain our commitment to protecting adolescents' fragile mental health, and can help them develop into a healthy, fulfilling and contributing adult life.

Olfactory Impairment Is the Main Predictor of Higher Scores at REM Sleep Behavior Disorder (RBD) Screening Questionnaire in Parkinson's Disease Patients.

INTRODUCTION: Olfactory impairment and REM sleep behavior disorder (RBD) are common non-motor symptoms in Parkinson's disease (PD) patients, often preceding the onset of the specific motor symptoms and, thus, crucial for strategies directed to anticipate PD diagnosis. In this context, the specific interaction between olfactory impairment and RBD has not been clearly defined. OBJECTIVE: The aim of this study was to determine the possible role of olfactory impairment and other clinical characteristics as possible predictors of higher scores at RBD screening questionnaire (RBDSQ) in a large population of PD patients. METHODS: In this study, 590 PD patients were included from the Parkinson's Progression Markers Initiative. Demographic and clinical features were registered. All participants completed motor and non-motor evaluations at the baseline visit. For motor assessments, the disease severity was evaluated by the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) pars III. Regarding non-motor symptoms assessment, Montreal Cognitive Assessments (MoCA), University of Pennsylvania Smell Identification Test (UPSIT) and RBD screening questionnaire (RBDSQ) were registered. RESULTS: Among 590 PD patients included in this study, 111 patients with possible RBD were found (18.8%). RBD was less frequent in female PD patients (p ≤ 0.011). Among patients with or without possible RBD diagnosis, statistically significant differences in MDS-UPDRS III (23.3 ± 11.4 vs. 19.7 ± 9.1, respectively, p ≤ 0.002) and in UPSIT score (19.7 ± 8.3 vs. 22.6 ± 8.0, respectively, p ≤ 0.001) were found. Moreover, significant correlations between RBDSQ versus UPDRS III score and versus UPSIT score were observed. Multivariate linear regression analysis showed that UPSIT was the most significant predictor of higher scores at RBDSQ, while the other significant predictors were UPDRS III and age. CONCLUSIONS: The severity of olfactory impairment appears tightly correlated to RBD symptoms, highlighting the role of these biomarkers for PD patients. Additionally, according to this large study, our data confirmed that RBD in PD patients exhibits peculiar gender differences.

Improving stress management, anxiety, and mental well-being in medical students through an online Mindfulness-Based Intervention: a randomized study.

Pressures and responsibilities of medical school put a strain on medical student's personal wellbeing, leading among all to high rates of anxiety, emotional discomfort and stress. In this work we evaluated the effectiveness of a comprehensive Mindfulness-Based Intervention (MBI) in reducing this load. The intervention comprised 10 twice-a-week Integral Meditation classes, dietary advice, and brief yoga sessions. We performed a randomized trial on two cohort of medical students from Italian universities: 239 in cohort 1 (106 treated and 133 controls), and 123 in cohort 2 (68 treated and 55 control) for a total sample of 362 students. Nine questionnaires for evaluating the effectiveness of our intervention on stress (PSS), state anxiety (STAIX-1), well-being (WEMWBS), mind-wandering (MW-S), overall distress (PANAS), emotion regulation (DERS), resilience (RS-14), and attentional control (ACS-C and ACS-D) were collected both pre and post intervention. Linear mixed effect models were run on the whole sample showing that, after multiple testing correction, our intervention was effective in reducing perceived stress (ß = - 2.57 [- 4.02; - 1.12], p = 0.004), improving mental well-being (ß = 2.82 [1.02; 4.63], p = 0.008) and emotional regulation (ß = - 8.24 [- 12.98; - 3.51], p = 0.004), resilience (ß = 3.79 [1.32; 6.26], p = 0.008), reducing the tendency to wander with the mind (ß = - 0.70 [- 0.99; - 0.39], p = 0.0001), ameliorating the ability to maintain attention (AC-S (ß = - 0.23 [- 0.44; - 0.02], p = 0.04) and AC-D (ß = - 0.19 [- 0.36; - 0.01], p = 0.04)), and the overall distress (ß = 1.84 [0.45; 3.23], p = 0.02).

Blood-Based Biomarkers for Alzheimer's Disease Diagnosis and Progression: An Overview.

Alzheimer's Disease (AD) is a progressive neurodegenerative disease characterized by amyloid-ß (Aß) plaque deposition and neurofibrillary tangle accumulation in the brain. Although several studies have been conducted to unravel the complex and interconnected pathophysiology of AD, clinical trial failure rates have been high, and no disease-modifying therapies are presently available. Fluid biomarker discovery for AD is a rapidly expanding field of research aimed at anticipating disease diagnosis and following disease progression over time. Currently, Aß1-42, phosphorylated tau, and total tau levels in the cerebrospinal fluid are the best-studied fluid biomarkers for AD, but the need for novel, cheap, less-invasive, easily detectable, and more-accessible markers has recently led to the search for new blood-based molecules. However, despite considerable research activity, a comprehensive and up-to-date overview of the main blood-based biomarker candidates is still lacking. In this narrative review, we discuss the role of proteins, lipids, metabolites, oxidative-stress-related molecules, and cytokines as possible disease biomarkers. Furthermore, we highlight the potential of the emerging miRNAs and long non-coding RNAs (lncRNAs) as diagnostic tools, and we briefly present the role of vitamins and gut-microbiome-related molecules as novel candidates for AD detection and monitoring, thus offering new insights into the diagnosis and progression of this devastating disease.

Pathophysiology and Therapy of High-Altitude Sickness: Practical Approach in Emergency and Critical Care.

High altitude can be a hostile environment and a paradigm of how environmental factors can determine illness when human biological adaptability is exceeded. This paper aims to provide a comprehensive review of high-altitude sickness, including its epidemiology, pathophysiology, and treatments. The first section of our work defines high altitude and considers the mechanisms of adaptation to it and the associated risk factors for low adaptability. The second section discusses the main high-altitude diseases, highlighting how environmental factors can lead to the loss of homeostasis, compromising important vital functions. Early recognition of clinical symptoms is important for the establishment of the correct therapy. The third section focuses on high-altitude pulmonary edema, which is one of the main high-altitude diseases. With a deeper understanding of the pathogenesis of high-altitude diseases, as well as a reasoned approach to environmental or physical factors, we examine the main high-altitude diseases. Such an approach is critical for the effective treatment of patients in a hostile environment, or treatment in the emergency room after exposure to extreme physical or environmental factors.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): An Overview.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic systemic disease that manifests via various symptoms such as chronic fatigue, post-exertional malaise, and cognitive impairment described as "brain fog". These symptoms often prevent patients from keeping up their pre-disease onset lifestyle, as extended periods of physical or mental activity become almost impossible. However, the disease presents heterogeneously with varying severity across patients. Therefore, consensus criteria have been designed to provide a diagnosis based on symptoms. To date, no biomarker-based tests or diagnoses are available, since the molecular changes observed also largely differ from patient to patient. In this review, we discuss the infectious, genetic, and hormonal components that may be involved in CFS pathogenesis, we scrutinize the role of gut microbiota in disease progression, we highlight the potential of non-coding RNA (ncRNA) for the development of diagnostic tools and briefly mention the possibility of SARS-CoV-2 infection causing CFS.

Clinical Significance of Myelin Oligodendrocyte Glycoprotein Autoantibodies in Patients with Typical MS Lesions on MRI.

BACKGROUND: Myelin-oligodendrocyte-glycoprotein (MOG)-IgG-positivity in patients with typical MS lesions on MRI may lead to diagnostic/therapeutic uncertainty. OBJECTIVE AND METHODS: We reviewed reports of cases with MS phenotype on MRI and MOG-IgG-positivity published in Pubmed between 01/2012-06/2021. RESULTS: Sixteen patients were included (median age [range], 37,5 [25-66] years; 60% female). Three patients initially tested negative for MOG-IgG. Disease course was: relapsing-remitting, 10; or progressive, 6. Intrathecal IgG-synthesis was common (79%). Low and high-efficacy MS-targeted agents prevented relapses in 30% and 100%, respectively. None of the patients showed resolution of MRI T2-lesions over time. CONCLUSIONS: MOG-IgG-positivity is unlikely to alter the expected treatment response and outcomes in patients with otherwise typical MS phenotype on MRI.

The Reliability of Anamnestic Data in the Management of Clostridium Tetani Infection in Elderly.

Background: Tetanus infection remains a significant complication of wounds. Because most tetanus treatment guidelines rely on anamnestic data collected directly from patients, the congruence between anamnesis and laboratory evidence must be verified, especially in the elderly population. Aim: Assess, in both the geriatric population (>65) and the non-geriatric one, the reliability of anamnestic data for managing patients with tetanus-risk wounds, identified categories of populations most exposed to non-vaccination coverage, and assessed the agreement of the Tetanos Quick Stick (TQS) results with the therapy performed (administration of tetanus vaccine or immunoglobulin). Methods: In this retrospective single-center observational study, patients were asked their immunization status against tetanus vaccination. The decision to administer a vaccine or immunoglobulin was therefore clinical and based on anamnestic criteria. The TQS test was then given to patients who were unaware of their immunity status. Patients who thought they knew it but were not sure were given the TQS test to determine whether the anamnestic collection was supported by the test. The TQS test results were compared with the anamnestic data. Results: Most patients, geriatric and not geriatric, did not know their immune status. Among those who reported knowing their immune status, there was no agreement between the vaccine coverage declared by patients and the TQS test results (p < 0.001), mainly in geriatric patients but also in the control group. Elderly and women had significantly lower positive TQS test results (p < 0.001). There was a statistically significant discrepancy (p < 0.001) between the therapy based on anamnestic data and the TQS test results. Conclusion: The reliability of anamnestic data for the management of patients with tetanus-risk wounds is low and decreases with age, becoming minimal in geriatric patients. Elderly and women are less likely to have an effective vaccination status against tetanus.