Comorbidity in myasthenia gravis: multicentric, hospital-based, and controlled study of 178 Italian patients.

BACKGROUND: Myasthenia gravis (MG) is an autoimmune disorder with fluctuating weakness that causes significant disability and morbidity. Comorbidities may influence the course of MG, particularly in specific subgroups. The aim of this study is to investigate the frequency of comorbidities in MG patients compared to healthy controls (HC) and to evaluate their distribution according to age at disease onset, sex, and disease severity. METHODS: MG patients attending the University Hospital "Paolo Giaccone" in Palermo and "SS Annunziata" Hospital in Chieti were enrolled; HC were enrolled from the general population. Non-parametric statistics and logistic regression were used to assess the association of specific comorbidities according to age at disease onset, sex, disease subtypes, and severity of the disease. RESULTS: A total of 356 subjects were included in the study: 178 MG patients (46% F; median age 60 years [51-71]) and 178 sex- and age-matched HC (46% F, median age 59 years [50-66]). Overall, 86% of MG patients and 76% of HC suffered from comorbidities, and MG patients had a higher number of comorbidities compared to HC. Patients with late-onset suffered from more comorbidities than those with early-onset MG. Hypertension was more common in male patients with MG, while thymic hyperplasia, osteoporosis, and autoimmune diseases were more common in females. Respiratory disorders and thymoma were more common in patients with more severe disease (p < 0.05 for all comparisons). CONCLUSION: MG patients, particularly those with late onset, showed a higher prevalence of comorbidities than HC. Assessment of comorbidities in MG is an essential issue to identify the appropriate treatment and achieve the best management.

Pathophysiology of multiple sclerosis damage and repair: Linking cerebral hypoperfusion to the development of irreversible tissue loss in multiple sclerosis using magnetic resonance imaging.

BACKGROUND AND PURPOSE: Reduced cerebral perfusion has been observed in multiple sclerosis (MS) and may contribute to tissue loss both acutely and chronically. Here, we test the hypothesis that hypoperfusion occurs in MS and relates to the presence of irreversible tissue damage. METHODS: In 91 patients with relapsing MS and 26 healthy controls (HC), gray matter (GM) cerebral blood flow (CBF) was assessed using pulsed arterial spin labeling. GM volume, T1 hypointense and T2 hyperintense lesion volumes (T1LV and T2LV, respectively), and the proportion of T2-hyperintense lesion volume that appears hypointense on T1-weighted magnetic resonance imaging (T1LV/T2LV) were quantified. GM CBF and GM volume were evaluated globally, as well as regionally, using an atlas-based approach. RESULTS: Global GM CBF was lower in patients (56.9 ± 12.3 mL/100 g/min) than in HC (67.7 ± 10.0 mL/100 g/min; p < 0.001), a difference that was widespread across brain regions. Although total GM volume was comparable between groups, significant reductions were observed in a subset of subcortical structures. GM CBF negatively correlated with T1LV (r = -0.43, p = 0.0002) and T1LV/T2LV (r = -0.37, p = 0.0004), but not with T2LV. CONCLUSIONS: GM hypoperfusion occurs in MS and is associated with irreversible white matter damage, thus suggesting that cerebral hypoperfusion may actively contribute and possibly precede neurodegeneration by hampering tissue repair abilities in MS.

Functional Neurologic Disorders, disorders to be managed by neurologists, or are neurologists wandering in a dangerous field with inadequate resources?

In recent years, some neurologists reconsidered their approach to Medically Unexplained Symptoms and proposed Functional Neurologic Disorders (FND) as a new entity, claiming that neurology could offer alternative treatment options to the psychotherapies provided in psychiatry settings. FNDs, for this purpose, should include only the disorders listed as Conversion from the Somatic Symptom and Related Disorders (SSRD) group. The present review analyzes the rationale of this position and challenges the arguments provided for its support. The review also discusses the systematization of these disorders as provided by public health systems. It outlines risks stemming from economic support and public funding uncertainty, given their negligible epidemiological dimensions resulting from the parcellation of SSRD. The review underlines the unresolved issue of Factitious Disorders, which are in the same SSRD category of the international classification but are, nonetheless, overlooked by the theoretical proponents of the FND entity. Comorbidity with other psychiatric disorders is also analyzed. We propose a model that supports the continuum between different SSRD conditions, including Factitious Disorders. The model is based on the emergence of feigned death reflex and deception from frontal lobe dysfunction. Finally, the paper summarizes the wealth of historical psychiatric and psychodynamic approaches and critical reviews. The study also puts in context the categorization and interpretation efforts provided by the most eminent researchers of the past century.

Adherence and Reactogenicity to Vaccines against SARS-COV-2 in 285 Patients with Neuropathy: A Multicentric Study.

Background: The safety of the new vaccines against SARS-CoV-2 have already been shown, although data on patients with polyneuropathy are still lacking. The aim of this study is to evaluate the adherence to SARS-CoV-2 vaccination, as well as the reactogenicity to those vaccines in patients affected by neuropathy. Methods: A multicentric and web-based cross-sectional survey was conducted among patients affected by neuropathy from part of South Italy. Results: Out of 285 responders, n = 268 were included in the final analysis and n = 258 of them (96.3%) were fully vaccinated. Adherence to vaccination was higher in patients with hereditary neuropathies compared to others, while it was lower in patients with anti-MAG neuropathy (all p < 0.05). The overall prevalence of adverse events (AEs) was 61.2% and its occurrence was not associated with neuropathy type. Being female and of younger age were factors associated with higher risk of AEs, while having an inflammatory neuropathy and steroids assumption were associated with a lower risk (all p < 0.05). Younger age, having had an AE, and COVID-19 before vaccination were factors associated with symptoms worsening after vaccination (all p < 0.05). (4) Conclusions: Patients with neuropathy showed a high level of adherence to COVID-19 vaccination. Safety of vaccines in patients with neuropathies was comparable to the general population and it was more favorable in those with inflammatory neuropathy.

Cerebrovascular reactivity in multiple sclerosis is restored with reduced inflammation during immunomodulation.

Cerebrovascular reactivity (CVR) reflects the capacity of the brain's vasculature to increase blood flow following a vasodilatory stimulus. Reactivity is an essential property of the brain's blood vessels that maintains nutrient supplies in the face of changing demand. In Multiple Sclerosis (MS), CVR may be diminished with brain inflammation and this may contribute to neurodegeneration. We test the hypothesis that CVR is altered with MS neuroinflammation and that it is restored when inflammation is reduced. Using a breath-hold task during functional Magnetic Resonance Imaging (MRI), we mapped grey matter and white matter CVRs (CVRGM and CVRWM, respectively) in 23 young MS patients, eligible for disease modifying therapy, before and during Interferon beta treatment. Inflammatory activity was inferred from the presence of Gadolinium enhancing lesions at MRI. Eighteen age and gender-matched healthy controls (HC) were also assessed. Enhancing lesions were observed in 12 patients at the start of the study and in 3 patients during treatment. Patients had lower pre-treatment CVRGM (p = 0.04) and CVRWM (p = 0.02) compared to HC. In patients, a lower pre-treatment CVRGM was associated with a lower GM volume (r = 0.60, p = 0.003). On-treatment, there was an increase in CVRGM (p = 0.02) and CVRWM (p = 0.03) that negatively correlated with pre-treatment CVR (GM: r = - 0.58, p = 0.005; WM: r = - 0.60, p = 0.003). CVR increased when enhancing lesions reduced in number (GM: r = - 0.48, p = 0.02, WM: r = - 0.62, p = 0.003). Resolution of inflammation may restore altered cerebrovascular function limiting neurodegeneration in MS. Imaging of cerebrovascular function may thereby inform tissue physiology and improve treatment monitoring.

Bipolar spectrum disorders in neurologic disorders.

Psychiatric symptoms frequently predate or complicate neurological disorders, such as neurodegenerative diseases. Symptoms of bipolar spectrum disorders (BSD), like mood, behavioral, and psychotic alterations, are known to occur - individually or as a syndromic cluster - in Parkinson's disease and in the behavioral variant of frontotemporal dementia (FTD). Nonetheless, due to shared pathophysiological mechanisms, or genetic predisposition, several other neurological disorders show significant, yet neglected, clinical and biological overlaps with BSD like neuroinflammation, ion channel dysfunctions, neurotransmission imbalance, or neurodegeneration. BSD pathophysiology is still largely unclear, but large-scale network dysfunctions are known to participate in the onset of mood disorders and psychotic symptoms. Thus, functional alterations can unleash BSD symptoms years before the evidence of an organic disease of the central nervous system. The aim of our narrative review was to illustrate the numerous intersections between BSD and neurological disorders from a clinical-biological point of view and the underlying predisposing factors, to guide future diagnostic and therapeutical research in the field.

The factitious/malingering continuum and its burden on public health costs: a review and experience in an Italian neurology setting.

Factitious disorder is classified as one of the five aspects of somatic symptom disorders. The fundamental element of factitious disorder is deception, i.e., pretending to have a medical or psychiatric disorder, but the enactment of deception is considered unconscious. Indeed, volition, i.e., the perception of deliberate deception, is blurred in patients presenting with factitious disorder. In the USA and the UK, factitious disorder has received constant media attention because of its forensic implications and outrageous costs for the National Health Systems. Unfortunately, a comparable level of attention is not present in Italian National Health System or the Italian mass media. The review analyzes the classifications, disorder mechanisms, costs, and medico-legal implications in the hope of raising awareness on this disturbing issue. Moreover, the review depicts 13 exemplification cases, anonymized and fictionalized by expert writers. Finally, our paper also evaluates the National Health System's expenditures for each patient, outlandish costs in the range between 50,000 and 1 million euros.

Diabetes Mellitus and Amyotrophic Lateral Sclerosis: A Systematic Review.

BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a degenerative disorder which affects the motor neurons. Growing evidence suggests that ALS may impact the metabolic system, including the glucose metabolism. Several studies investigated the role of Diabetes Mellitus (DM) as risk and/or prognostic factor. However, a clear correlation between DM and ALS has not been defined. In this review, we focus on the role of DM in ALS, examining the different hypotheses on how perturbations of glucose metabolism may interact with the pathophysiology and the course of ALS. METHODS: We undertook an independent PubMed literature search, using the following search terms: ((ALS) OR (Amyotrophic Lateral Sclerosis) OR (Motor Neuron Disease)) AND ((Diabetes) OR (Glucose Intolerance) OR (Hyperglycemia)). Review and original articles were considered. RESULTS: DM appears not to affect ALS severity, progression, and survival. Contrasting data suggested a protective role of DM on the occurrence of ALS in elderly and an opposite effect in younger subjects. CONCLUSIONS: The actual clinical and pathophysiological correlation between DM and ALS is unclear. Large longitudinal prospective studies are needed. Achieving large sample sizes comparable to those of common complex diseases like DM is a challenge for a rare disease like ALS. Collaborative efforts could overcome this specific issue.

Agitation and Dementia: Prevention and Treatment Strategies in Acute and Chronic Conditions.

Agitation is a behavioral syndrome characterized by increased, often undirected, motor activity, restlessness, aggressiveness, and emotional distress. According to several observations, agitation prevalence ranges from 30 to 50% in Alzheimer's disease, 30% in dementia with Lewy bodies, 40% in frontotemporal dementia, and 40% in vascular dementia (VaD). With an overall prevalence of about 30%, agitation is the third most common neuropsychiatric symptoms (NPS) in dementia, after apathy and depression, and it is even more frequent (80%) in residents of nursing homes. The pathophysiological mechanism underlying agitation is represented by a frontal lobe dysfunction, mostly involving the anterior cingulate cortex (ACC) and the orbitofrontal cortex (OFC), respectively, meaningful in selecting the salient stimuli and subsequent decision-making and behavioral reactions. Furthermore, increased sensitivity to noradrenergic signaling has been observed, possibly due to a frontal lobe up-regulation of adrenergic receptors, as a reaction to the depletion of noradrenergic neurons within the locus coeruleus (LC). Indeed, LC neurons mainly project toward the OFC and ACC. These observations may explain the abnormal reactivity to weak stimuli and the global arousal found in many patients who have dementia. Furthermore, agitation can be precipitated by several factors, e.g., the sunset or low lighted environments as in the sundown syndrome, hospitalization, the admission to nursing residencies, or changes in pharmacological regimens. In recent days, the global pandemic has increased agitation incidence among dementia patients and generated higher distress levels in patients and caregivers. Hence, given the increasing presence of this condition and its related burden on society and the health system, the present point of view aims at providing an extensive guide to facilitate the identification, prevention, and management of acute and chronic agitation in dementia patients.

Unusual Presentation of Bilateral Carotid Artery Dissection: The Importance of Reasoning Outside the Box.

A bilateral internal carotid artery dissection presenting with atypical symptoms of cerebral hypoperfusion has been rarely reported, especially in the absence of obvious precipitating factors. A middle-aged woman presented to the emergency department with a 2-day-history of progressive left arm numbness and weakness, confusion, disorientation and clumsiness worsened by upright position. A cerebral hypoperfusion condition was hypothesized and confirmed by a CT angiography, which showed bilateral internal carotid dissection with uncertain etiology. Screening for predisposing conditions to spontaneous carotid arteries dissection was basically negative. Regarding potential precipitating factors, the patient had used an electric olive harvester days before symptoms onset, without any painful sensation or sudden sequelae. Portable harvesters in olive growing transmit vibrations to the hand-arm system but it remains to be elucidated if hand-arm vibrations can be implicated in vessels wall injury and dissection. Bilateral carotid artery dissection is an infrequent and life-threatening condition which can rarely present with non-specific symptoms of cerebral hypoperfusion. The absence of typical symptoms and known precipitating factors can made the diagnosis quite hard to achieve.