The Lack of Ad Hoc Neuropsychological Assessment in Adults with Neurofibromatosis: A Systematic Review.

Background: Neurofibromatosis Type 1 (NF1) is a genetic autosomal dominant disorder that affects both the central and peripheral nervous systems. Children and adolescents with NF1 commonly experience neuropsychological, motor, and behavioral deficits. The cognitive profile hallmark of this disorder includes visuospatial and executive function impairments. These cognitive disorders may persist into adulthood. This study aims to analyze previous research studies that have described cognitive dysfunctions in adults with NF1. The purpose of this analysis is to review the neuropsychological and psychological assessment methods used. Methods: A total of 327 articles were identified based on the search terms in their titles and abstracts. The evaluation was conducted by scrutinizing each article's title, abstract, and text. Results: Only 16 articles were found to be eligible for inclusion based on the pre-defined criteria. The selected studies primarily focus on the development of diagnostic protocols for individuals with NF1. Conclusions: The management of NF1 disease requires a multidisciplinary approach to address symptoms, preserve neurological functions, and ensure the best possible quality of life. However, cognitive impairment can negatively affect psychological well-being. This study suggested that cognitive functions in NF1 patients were not tested using specific measures, but rather were evaluated through intelligence scales. Additionally, the findings revealed that there is no standardized neuropsychological assessment for adults with NF1. To address this gap, it would be helpful to create a specific neuropsychological battery to study cognitive function in NF1 patients during clinical studies. This battery could also serve as a tool to design models for cognitive rehabilitation by using reliable and sensitive measures of cognitive outcomes.

Classical cannabinoid receptors as target in cancer-induced bone pain: a systematic review, meta-analysis and bioinformatics validation.

To test the hypothesis that genetic and pharmacological modulation of the classical cannabinoid type 1 (CB1) and 2 (CB2) receptors attenuate cancer-induced bone pain, we searched Medline, Web of Science and Scopus for relevant skeletal and non-skeletal cancer studies from inception to July 28, 2022. We identified 29 animal and 35 human studies. In mice, a meta-analysis of pooled studies showed that treatment of osteolysis-bearing males with the endocannabinoids AEA and 2-AG (mean difference [MD] - 24.83, 95% confidence interval [95%CI] - 34.89, - 14.76, p < 0.00001) or the synthetic cannabinoid (CB) agonists ACPA, WIN55,212-2, CP55,940 (CB1/2-non-selective) and AM1241 (CB2-selective) (MD - 28.73, 95%CI - 45.43, - 12.02, p = 0.0008) are associated with significant reduction in paw withdrawal frequency. Consistently, the synthetic agonists AM1241 and JWH015 (CB2-selective) increased paw withdrawal threshold (MD 0.89, 95%CI 0.79, 0.99, p < 0.00001), and ACEA (CB1-selective), AM1241 and JWH015 (CB2-selective) reduced spontaneous flinches (MD - 4.85, 95%CI - 6.74, - 2.96, p < 0. 00001) in osteolysis-bearing male mice. In rats, significant increase in paw withdrawal threshold is associated with the administration of ACEA and WIN55,212-2 (CB1/2-non-selective), JWH015 and AM1241 (CB2-selective) in osteolysis-bearing females (MD 8.18, 95%CI 6.14, 10.21, p < 0.00001), and treatment with AM1241 (CB2-selective) increased paw withdrawal thermal latency in males (mean difference [MD]: 3.94, 95%CI 2.13, 5.75, p < 0.0001), confirming the analgesic capabilities of CB1/2 ligands in rodents. In human, treatment of cancer patients with medical cannabis (standardized MD - 0.19, 95%CI - 0.35, - 0.02, p = 0.03) and the plant-derived delta-9-THC (20 mg) (MD 3.29, CI 2.24, 4.33, p < 0.00001) or its synthetic derivative NIB (4 mg) (MD 2.55, 95%CI 1.58, 3.51, p < 0.00001) are associated with reduction in pain intensity. Bioinformatics validation of KEGG, GO and MPO pathway, function and process enrichment analysis of mouse, rat and human data revealed that CB1 and CB2 receptors are enriched in a cocktail of nociceptive and sensory perception, inflammatory, immune-modulatory, and cancer pathways. Thus, we cautiously conclude that pharmacological modulators of CB1/2 receptors show promise in the treatment of cancer-induced bone pain, however further assessment of their effects on bone pain in genetically engineered animal models and cancer patients is warranted.

Abaloparatide is more potent than teriparatide in restoring bone mass and strength in type 1 diabetic male mice.

This study investigated the efficacy of the two FDA-approved bone anabolic ligands of the parathyroid hormone receptor 1 (PTH1R), teriparatide or human parathyroid hormone 1-34 (PTH) and abaloparatide (ABL), to restoring skeletal health using a preclinical murine model of streptozotocin-induced T1-DM. Intermittent daily subcutaneous injections of equal molar doses (12 pmoles/g/day) of PTH (50 ng/g/day), ABL (47.5 ng/g/day), or vehicle, were administered for 28 days to 5-month-old C57Bl/6 J male mice with established T1-DM or control (C) mice. ABL was superior to PTH in increasing or restoring bone mass in control or T1-MD mice, respectively, which was associated with superior stimulation of trabecular and periosteal bone formation, upregulation of osteoclastic/osteoblastic gene expression, and increased circulating bone remodeling markers. Only ABL corrected the reduction in ultimate load, which is a measure of bone strength, induced by T1-DM, and it also increased energy to ultimate load. In addition, bones from T1-DM mice treated with PTH or ABL exhibited increased ultimate stress, a material index, compared to T1-DM mice administered with vehicle. And both PTH and ABL prevented the increased expression of the Wnt antagonist Sost/sclerostin displayed by T1-DM mice. Further, PTH and ABL increased to a similar extent the circulating bone resorption marker CTX and the bone formation marker P1NP in T1-DM after 2 weeks of treatment; however, only ABL sustained these increases after 4 weeks of treatment. We conclude that at equal molar doses, ABL is more effective than PTH in increasing bone mass and restoring the cortical and trabecular bone lost with T1-DM, due to higher and longer-lasting increases in bone remodeling.

Neuroinflammaging: A Tight Line Between Normal Aging and Age-Related Neurodegenerative Disorders.

Aging in the healthy brain is characterized by a low-grade, chronic, and sterile inflammatory process known as neuroinflammaging. This condition, mainly consisting in an up-regulation of the inflammatory response at the brain level, contributes to the pathogenesis of age-related neurodegenerative disorders. Development of this proinflammatory state involves the interaction between genetic and environmental factors, able to induce age-related epigenetic modifications. Indeed, the exposure to environmental compounds, drugs, and infections, can contribute to epigenetic modifications of DNA methylome, histone fold proteins, and nucleosome positioning, leading to epigenetic modulation of neuroinflammatory responses. Furthermore, some epigenetic modifiers, which combine and interact during the life course, can contribute to modeling of epigenome dynamics to sustain, or dampen the neuroinflammatory phenotype. The aim of this review is to summarize current knowledge about neuroinflammaging with a particular focus on epigenetic mechanisms underlying the onset and progression of neuroinflammatory cascades in the central nervous system; furthermore, we describe some diagnostic biomarkers that may contribute to increase diagnostic accuracy and help tailor therapeutic strategies in patients with neurodegenerative diseases.

Magnetic Resonance Imaging in Preterm Infant: A Systematic Review on Clinical Procedure Safety.

BACKGROUND: Currently, there is no evidence that MRI produces harmful effects on premature newborns, as well as short-term and long-term safety issues regarding radiofrequency fields and loud acoustic environment, while the examination that is being performed has not been clearly investigated. MRI of the brain conducted on preterm infants should be part of the diagnostic workup, when necessary. This article is intended to evaluate the short-term safety of MRI performed in preterm infants, when required, by analyzing all vital parameters available before, during, and after the MRI procedures. METHODS: We conducted a systematic review of the literature on electronic medical databases (PubMed and ClinicalTrials.gov) following the Preferred Reported Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We included all preterm infants who underwent MRI whose clinical, hemodynamic, and respiratory parameters were reported. The quality of the included articles was assessed using QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies) tool. RESULTS: Six studies were included with a total of 311 preterm infants. No severe adverse event, such as death, occurred during MRI procedures. Vital signs remained stable in about two-thirds of all patients. CONCLUSIONS: Given the general clinical safety of MRI, we suggest it as a tool to be used in preterm infants in Neonatal Intensive Care Units, when necessary. We further suggest the development of standard protocols to guide the use of MRI in preterm infants to maximize the clinical safety of the procedure.

Applications of Artificial Intelligence in the Neuropsychological Assessment of Dementia: A Systematic Review.

In the context of advancing healthcare, the diagnosis and treatment of cognitive disorders, particularly Mild Cognitive Impairment (MCI) and Alzheimer's Disease (AD), pose significant challenges. This review explores Artificial Intelligence (AI) and Machine Learning (ML) in neuropsychological assessment for the early detection and personalized treatment of MCI and AD. The review includes 37 articles that demonstrate that AI could be an useful instrument for optimizing diagnostic procedures, predicting cognitive decline, and outperforming traditional tests. Three main categories of applications are identified: (1) combining neuropsychological assessment with clinical data, (2) optimizing existing test batteries using ML techniques, and (3) employing virtual reality and games to overcome the limitations of traditional tests. Despite advancements, the review highlights a gap in developing tools that simplify the clinician's workflow and underscores the need for explainable AI in healthcare decision making. Future studies should bridge the gap between technical performance measures and practical clinical utility to yield accurate results and facilitate clinicians' roles. The successful integration of AI/ML in predicting dementia onset could reduce global healthcare costs and benefit aging societies.

Circulating biomarkers in familial cerebral cavernous malformation.

BACKGROUND: Cerebral Cavernous Malformation (CCM) is a rare cerebrovascular disease, characterized by the presence of multiple vascular malformations that may result in intracerebral hemorrhages (ICHs), seizure(s), or focal neurological deficits (FND). Familial CCM (fCCM) is due to loss of function mutations in one of the three independent genes KRIT1 (CCM1), Malcavernin (CCM2), or Programmed Cell death 10 (PDCD10/CCM3). The aim of this study was to identify plasma protein biomarkers of fCCM to assess the severity of the disease and predict its progression. METHODS: Here, we have investigated plasma samples derived from n = 71 symptomatic fCCM patients (40 female/31 male) and n = 17 healthy donors (HD) (9 female/8 male) of the Phase 1/2 Treat_CCM trial, using multiplexed protein profiling approaches. FINDINGS: Biomarkers as sCD14 (p = 0.00409), LBP (p = 0.02911), CXCL4 (p = 0.038), ICAM-1 (p = 0.02013), ANG2 (p = 0.026), CCL5 (p = 0.00403), THBS1 (p = 0.0043), CRP (p = 0.0092), and HDL (p = 0.027), were significantly different in fCCM compared to HDs. Of note, sENG (p = 0.011), THBS1 (p = 0.011) and CXCL4 (p = 0.011), were correlated to CCM genotype. sROBO4 (p = 0.014), TM (p = 0.026) and CRP (p = 0.040) were able to predict incident adverse clinical events, such as ICH, FND or seizure. GDF-15, FLT3L, CXCL9, FGF-21 and CDCP1, were identified as predictors of the formation of new MRI-detectable lesions over 2-year follow-up. Furthermore, the functional relevance of ang2, thbs1, robo4 and cdcp1 markers was validated by zebrafish pre-clinical model of fCCM. INTERPRETATION: Overall, our study identifies a set of biochemical parameters to predict CCM progression, suggesting biological interpretations and potential therapeutic approaches to CCM disease. FUNDING: Italian Medicines Agency, Associazione Italiana per la Ricerca sul Cancro (AIRC), ERC, Leducq Transatlantic Network of Excellence, Swedish Research Council.

Changes in cerebral cortex activity during a simple motor task after MRgFUS treatment in patients affected by essential tremor and Parkinson's disease: a pilot study using functional NIRS.

Objective.Magnetic resonance imaging-guided focused ultrasound surgery (MRgFUS) is a non-invasive thermal ablation method that involves high-intensity focused ultrasound surgery (FUS) and Magnetic Resonance Imaging for anatomical imaging and real-time thermal mapping. This technique is widely employed for the treatment of patients affected by essential tremor (ET) and Parkinson's disease (PD). In the current study, functional near-infrared spectroscopy (fNIRS) was used to highlight hemodynamics changes in cerebral cortex activity, during a simple hand motor task, i.e. unimanual left and right finger-tapping, in ET and PD patients.Approach.All patients were evaluated before, one week and one month after MRgFUS treatment.Main results.fNIRS revealed cerebral hemodynamic changes one week and one month after MRgFUS treatment, especially in the ET group, that showed a significant clinical improvement in tremor clinical scores.Significance.To our knowledge, our study is the first that showed the use of fNIRS system to measure the cortical activity changes following unilateral ventral intermediate nucleus thalamotomy after MRgFUS treatment. Our findings showed that therapeutic MRgFUS promoted the remodeling of neuronal networks and changes in cortical activity in association with symptomatic improvements.

Pharmacologic targeting of the p62 ZZ domain enhances both anti-tumor and bone-anabolic effects of bortezomib in multiple myeloma.

Multiple myeloma (MM) is a malignancy of plasma cells whose antibody secretion creates proteotoxic stress relieved by the N-end rule pathway, a proteolytic system that degrades Narginylated proteins in the proteasome. When the proteasome is inhibited, protein cargo is alternatively targeted for autophagic degradation by binding to the ZZ-domain of p62/sequestosome-1. Here, we demonstrate that XRK3F2, a selective ligand for the ZZ-domain, dramatically improved two major responses to the proteasome inhibitor bortezomib by increasing: 1) killing of human MM cells by stimulating both bortezomib mediated apoptosis and necroptosis, a process regulated by p62; and 2) preservation of bone mass by stimulating osteoblasts differentiation and inhibiting osteoclastic bone destruction. Co-administration of bortezomib and XRK3F2 inhibited both branches of the bimodal N-end rule pathway exhibited synergistic anti-MM effects on MM cell lines and CD138+ cells from MM patients, and prevented stromal-mediated MM cell survival. In mice with established human MM, coadministration of bortezomib and XRK3F2 decreased tumor burden and prevented the progression of MM-induced osteolytic disease by inducing new bone formation more effectively than either single agent alone. The results suggest that p62-ZZ ligands enhance the anti-MM efficacy of proteasome inhibitors and can reduce MM morbidity and mortality by improving bone health.

MR-Guided Focused Ultrasound for Refractory Epilepsy: Where Are We Now?

Epilepsy is one of the most common neurological diseases in both adults and children. Despite improvements in medical care, 20 to 30% of patients are still resistant to the best medical treatment. The quality of life, neurologic morbidity, and even mortality of patients are significantly impacted by medically intractable epilepsy. Nowadays, conservative therapeutic approaches consist of increasing medication dosage, changing to a different anti-seizure drug as monotherapy, and combining different antiseizure drugs using an add-on strategy. However, such measures may not be sufficient to efficiently control seizure recurrence. Resective surgery, ablative procedures and non-resective neuromodulatory (deep-brain stimulation, vagus nerve stimulation) treatments are the available treatments for these kinds of patients. However, invasive procedures may involve lengthy inpatient stays for the patients, risks of long-term neurological impairment, general anesthesia, and other possible surgery-related complications (i.e., hemorrhage or infection). In the last few years, MR-guided focused ultrasound (MRgFUS) has been proposed as an emerging treatment for neurological diseases because of technological advancements and the goal of minimally invasive neurosurgery. By outlining the current knowledge obtained from both preclinical and clinical studies and discussing the technical opportunities of this therapy for particular epileptic phenotypes, in this perspective review, we explore the various mechanisms and potential applications (thermoablation, blood-brain barrier opening for drug delivery, neuromodulation) of high- and low-intensity ultrasound, highlighting possible novel strategies to treat drug-resistant epileptic patients who are not eligible or do not accept currently established surgical approaches. Taken together, the available studies support a possible role for lesional treatment over the anterior thalamus with high-intensity ultrasound and neuromodulation of the hippocampus via low-intensity ultrasound in refractory epilepsy. However, more studies, likely conceiving epilepsy as a network disorder and bridging together different scales and modalities, are required to make ultrasound delivery strategies meaningful, effective, and safe.

Coronavirus OC43 and Influenza H3N2 Concomitant Unilateral Parotitis: The Importance of Laboratory Tests in Mumps-Like Parotitis.

Mumps is an acute generalized infection caused by a Paramyxovirus. Infection occurs mainly in school-aged children and adolescents and the most prominent clinical manifestation is nonsuppurative swelling and tenderness of the salivary glands, unilaterally or bilaterally. Negative serology for mumps requires a differential diagnosis with other infectious agents, but it is not routine. An 11-year-old girl presented with fever and right-sided parotitis and a negative serology for Mumps. A respiratory panel revealed the presence of Coronavirus OC43 and influenza virus H3N2. Parotitis may be caused by the parainfluenza virus, Epstein-Barr virus, influenza virus, rhinovirus, adenovirus, or other viruses in addition to noninfectious causes such as drugs, immunologic diseases, or obstruction of the salivary tract as predisposing factors. In this case, Coronavirus OC43 and influenza virus H3N2 were detected. The H3N2 has been already reported in the literature, whereas Coronavirus OC43 has never been associated with parotitis before; although, in the present case, the association of the two viruses does not let us conclude which of the two was responsible for the disease.

Psychological symptoms in Multiple Sclerosis and the role of marital status: results from a retrospective single-center study.

BACKGROUND: Married people have, on average, better mental health than no married people. Psychological symptoms as anxiety and depression occur frequently in patients with multiple sclerosis (MS), increasing the severity of neurologic disability. The aim of this retrospective study was to investigate the relationship between functional disability and psychological symptoms differentiating by marital status. METHODS: In this study 150 MS outpatients without a history of psychological disorders were selected from the hospital database. The outpatient procedure for all patients includes the administration of the Expanded Disability Status Scale and the questionnaire Symptoms Checklist-90-Revised (SCL-90-R) a multidimensional self-report inventory, consisting of 90 items covering nine clinical dimensions: somatization (SOM), obsessive-compulsive (OC), interpersonal sensitivity (IS), depression (DEP), anxiety (ANX), hostility (HOS), phobic anxiety (PHOB), paranoid ideation (PAR), psychoticism (PSY), and three global indices of distress: global severity index (GSI), positive symptoms total (PST) and positive symptom distress index (PSDI). According to marital status, subjects were subdivided in single, married (including cohabitants), and divorced (including separated). A nonparametric group comparisons analysis was performed, as well as multivariate analysis which included generalized linear regression models. RESULTS: Regression results showed that functional disability was a significant predictor for all SCL- 90-R subscales. Moreover, it would seem that the single condition might be a protective factor for the development of psychological symptoms in SM patients. Notably, findings showed that younger subjects were predominantly single and had less psychological symptoms, whereas patients with greater psychological alterations were older in a stable affective couple relationship, presenting an elevation in depression, anxiety, somatization and compulsive, and obsessive scales. CONCLUSION: Numerous factors contribute to the onset of psychological disorders in multiple sclerosis. Marriage does not represent a protective factor for the development of psychological symptoms in SM patients. Future investigation is needed to ascertain the prevalence and underlying causes of psychological symptoms.

Paving the Way for Predicting the Progression of Cognitive Decline: The Potential Role of Machine Learning Algorithms in the Clinical Management of Neurodegenerative Disorders.

Alzheimer's disease (AD) is the most common form of neurodegenerative disorder. The prodromal phase of AD is mild cognitive impairment (MCI). The capacity to predict the transitional phase from MCI to AD represents a challenge for the scientific community. The adoption of artificial intelligence (AI) is useful for diagnostic, predictive analysis starting from the clinical epidemiology of neurodegenerative disorders. We propose a Machine Learning Model (MLM) where the algorithms were trained on a set of neuropsychological, neurophysiological, and clinical data to predict the diagnosis of cognitive decline in both MCI and AD patients. METHODS: We built a dataset with clinical and neuropsychological data of 4848 patients, of which 2156 had a diagnosis of AD, and 2684 of MCI, for the Machine Learning Model, and 60 patients were enrolled for the test dataset. We trained an ML algorithm using RoboMate software based on the training dataset, and then calculated its accuracy using the test dataset. RESULTS: The Receiver Operating Characteristic (ROC) analysis revealed that diagnostic accuracy was 86%, with an appropriate cutoff value of 1.5; sensitivity was 72%; and specificity reached a value of 91% for clinical data prediction with MMSE. CONCLUSION: This method may support clinicians to provide a second opinion concerning high prognostic power in the progression of cognitive impairment. The MLM used in this study is based on big data that were confirmed in enrolled patients and given a credibility about the presence of determinant risk factors also supported by a cognitive test score.

Neural Plasticity Changes Induced by Motor Robotic Rehabilitation in Stroke Patients: The Contribution of Functional Neuroimaging.

Robotic rehabilitation is one of the most advanced treatments helping people with stroke to faster recovery from motor deficits. The clinical impact of this type of treatment has been widely defined and established using clinical scales. The neurofunctional indicators of motor recovery following conventional rehabilitation treatments have already been identified by previous meta-analytic investigations. However, a clear definition of the neural correlates associated with robotic neurorehabilitation treatment has never been performed. This systematic review assesses the neurofunctional correlates (fMRI, fNIRS) of cutting-edge robotic therapies in enhancing motor recovery of stroke populations in accordance with PRISMA standards. A total of 7, of the initial yield of 150 articles, have been included in this review. Lessons from these studies suggest that neural plasticity within the ipsilateral primary motor cortex, the contralateral sensorimotor cortex, and the premotor cortices are more sensitive to compensation strategies reflecting upper and lower limbs' motor recovery despite the high heterogeneity in robotic devices, clinical status, and neuroimaging procedures. Unfortunately, the paucity of RCT studies prevents us from understanding the neurobiological differences induced by robotic devices with respect to traditional rehabilitation approaches. Despite this technology dating to the early 1990s, there is a need to translate more functional neuroimaging markers in clinical settings since they provide a unique opportunity to examine, in-depth, the brain plasticity changes induced by robotic rehabilitation.

A target discovery pipeline identified ILT3 as a target for immunotherapy of multiple myeloma.

Multiple myeloma (MM) is an incurable malignancy of plasma cells. To identify targets for MM immunotherapy, we develop an integrated pipeline based on mass spectrometry analysis of seven MM cell lines and RNA sequencing (RNA-seq) from 900+ patients. Starting from 4,000+ candidates, we identify the most highly expressed cell surface proteins. We annotate candidate protein expression in many healthy tissues and validate the expression of promising targets in 30+ patient samples with relapsed/refractory MM, as well as in primary healthy hematopoietic stem cells and T cells by flow cytometry. Six candidates (ILT3, SEMA4A, CCR1, LRRC8D, FCRL3, IL12RB1) and B cell maturation antigen (BCMA) present the most favorable profile in malignant and healthy cells. We develop a bispecific T cell engager targeting ILT3 that shows potent killing effects in vitro and decreased tumor burden and prolonged mice survival in vivo, suggesting therapeutic relevance. Our study uncovers MM-associated antigens that hold great promise for immune-based therapies of MM.

Incidence and Long-term Functional Outcome of Neurologic Disorders in Hospitalized Patients With COVID-19 Infected With Pre-Omicron Variants.

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.

Children under 6 years with acute headache in Pediatric Emergency Departments. A 2-year retrospective exploratory multicenter Italian study.

BACKGROUND: Preschool age (i.e. children under six years of age) represents a red flag for requiring neuroimaging to exclude secondary potentially urgent intracranial conditions (PUIC) in patients with acute headache. We investigated the clinical characteristics of preschoolers with headache to identify the features associated with a greater risk of secondary "dangerous" headache. METHODS: We performed a multicenter exploratory retrospective study in Italy from January 2017 to December 2018. Preschoolers with new-onset non-traumatic headache admitted to emergency department were included and were subsequently divided into two groups: hospitalized and discharged. Among hospitalized patients, we investigated the characteristics linked to potentially urgent intracranial conditions. RESULTS: We included 1455 preschoolers with acute headache. Vomiting, ocular motility disorders, ataxia, presence of neurological symptoms and signs, torticollis and nocturnal awakening were significantly associated to hospitalization. Among the 95 hospitalized patients, 34 (2.3%) had potentially urgent intracranial conditions and more frequently they had neurological symptoms and signs, papilledema, ataxia, cranial nerves paralysis, nocturnal awakening and vomiting. Nevertheless, on multivariable logistic regression analysis, we found that only ataxia and vomiting were associated with potentially urgent intracranial conditions. CONCLUSION: Our study identified clinical features that should be carefully evaluated in the emergency department in order to obtain a prompt diagnosis and treatment of potentially urgent intracranial conditions. The prevalence of potentially urgent intracranial conditions was low in the emergency department, which may suggest that age under six should not be considered an important risk factor for malignant causes as previously thought.

Need for palliative care from birth to infancy in pediatric patients with neurological diseases.

BACKGROUND: Palliative care is a comprehensive treatment approach that guarantees comfort for pediatric patients and their families from diagnosis to death. The techniques used for neurological patients in the field of palliative care can enhance the quality of care provided to patients with neurological disorders and support their families. PURPOSE: This study aimed to analyze the palliative care protocols in use in our department, describe the palliative course in the clinical setting, and propose the implementation of hospital palliative care for long-term prognosis of patients with neurological diseases. METHODS: This retrospective observational study examined the application of palliative care from birth to early infancy in neurological patients. We studied 34 newborns with diseases affecting the nervous system impairing prognosis. The study was conducted from 2016 to 2020 at the Neonatology Intensive Care Unit and the Pediatric Unit of the San Marco University Hospital in Catania, Sicily, Italy. RESULTS: Despite current legislation in Italy, no palliative care network has been activated to meet the needs of the population. In our center, given the vast number of patients with neurological conditions requiring palliative care, we should activate a straightforward departmental unit for neurologic pediatric palliative care. CONCLUSION: The establishment of specialized reference centers that manage significant neurological illnesses is due to neuroscience research progress in recent decades. Integration with specialized palliative care is sparse but now seems essential.