Maternal and fetal outcomes in an Italian multicentric cohort of women with multiple sclerosis exposed to dimethyl fumarate during pregnancy.

BACKGROUND: Evidence on the impact of dimethyl fumarate (DMF) during pregnancy in women with multiple sclerosis (MS) is limited. OBJECTIVES: To investigate disease activity and pregnancy outcomes in a retrospective cohort of women exposed to DMF in early pregnancy. METHODS: Women discontinuing DMF after pregnancy confirmation were identified from 29 Italian MS Centers. Disease activity 12 months before conception, during pregnancy, and 12 months postpartum were recorded, exploring reactivation predictors. Pregnancy and fetal outcomes were assessed. RESULTS: The study analyzed 137 pregnancies (12 pregnancy losses, 125 live births) from 137 women (mean age 32.9 ± 4.7 years), discontinuing DMF within a median (interquartile range (IQR)) interval of 4.9 (3.7-5.7) weeks from conception. In live birth pregnancies, annualized relapse rate (ARR) significantly decreased during pregnancy (ARR = 0.07, 95% confidence interval (CI): 0.03-0.14, p = 0.021) compared to pre-conception (ARR = 0.21 (95% CI: 0.14-0.30)) and increased postpartum ((ARR = 0.22 (95% CI: 0.15-0.32), p = 0.006). Median time to first relapse (TTFR) was 3.16 (IQR: 1:87-5.42) months. Higher pre-conception relapse number (hazard ratio (HR) = 2.33, 95% CI: 1.08-5.02) and Expanded Disability Status Scale (EDSS; HR = 1.81, 95% CI: 1.17-2.74) were associated with shorter TTFR, while treatment resumption with longer TTFR (HR = 0.29, 95% CI: 0.11-0.74). Fetal outcomes were unaffected by DMF exposure. CONCLUSION: DMF discontinuation does not increase relapse risk during pregnancy. Early therapy restart prevents postpartum relapses. Early DMF exposure shows no adverse fetal outcomes.

Tocilizumab treatment in MOGAD: a case report and literature review.

Myelin oligodendrocyte glycoprotein-immunoglobulin G associated disease (MOGAD) is an autoimmune demyelinating disorder of the central nervous system (CNS) which usually occurs with recurrent optic neuritis, transverse myelitis, acute disseminating encephalomyelitis, or brainstem encephalitis. To date, the anti-CD 20 drug rituximab (RTX) is employed in MOGAD although some authors reported the efficacy of Tocilizumab (TCZ) in refractory patients. We present the case of a woman affected by refractory MOGAD who was treated with TCZ after therapy with RTX had failed to prevent relapses. We also conducted a current literature review on TCZ use in MOGAD. A 57-year-old Caucasian woman affected by MOGAD with severe motor impairment and cognitive dysfunction was treated from 2020 to February 2022 with RTX. However, she experienced progressive clinical and cognitive worsening associated with white matter lesions mimicking leukodystrophy. In February 2022, the patient started therapy with TCZ administered with improvement of cognitive performance, walking ability, and brainstem functions. During TCZ, our patient reached the condition of NEDA-3 (no relapse, no increase in disability, no MRI activity on neuroimaging follow-up performed in September 2023). Moreover, the patient experienced paucisymptomatic SARS-CoV-2 infection that did not modify TCZ schedule. To date, there are few evidence on the efficacy and safety of TCZ in MOGAD. However, all the reviewed cases showed that TCZ represents an effective therapy in drug-resistant MOGAD. Our case highlights the efficacy of TCZ in drug resistant MOGAD and strengthens previous reports of TCZ safety and efficacy in MOGAD.

Involvement of the H3.3 Histone Variant in the Epigenetic Regulation of Gene Expression in the Nervous System, in Both Physiological and Pathological Conditions.

All the cells of an organism contain the same genome. However, each cell expresses only a minor fraction of its potential and, in particular, the genes encoding the proteins necessary for basal metabolism and the proteins responsible for its specific phenotype. The ability to use only the right and necessary genes involved in specific functions depends on the structural organization of the nuclear chromatin, which in turn depends on the epigenetic history of each cell, which is stored in the form of a collection of DNA and protein modifications. Among these modifications, DNA methylation and many kinds of post-translational modifications of histones play a key role in organizing the complex indexing of usable genes. In addition, non-canonical histone proteins (also known as histone variants), the synthesis of which is not directly linked with DNA replication, are used to mark specific regions of the genome. Here, we will discuss the role of the H3.3 histone variant, with particular attention to its loading into chromatin in the mammalian nervous system, both in physiological and pathological conditions. Indeed, chromatin modifications that mark cell memory seem to be of special importance for the cells involved in the complex processes of learning and memory.

Spinal cord compression in thoracolumbar burst fractures: application of high-definition three-dimensional exoscope in minimally invasive lateral surgery.

STUDY DESIGN: Spinal cord decompression in thoracolumbar burst fractures is challenging. Development of minimally invasive approaches and the improvement in new magnification technologies allowed a better and safer surgical treatment for these complex spinal injuries. We reported our experience in the minimally invasive surgical treatment of thoracolumbar burst fractures with spinal cord compression supported by high-definition (HD) three-dimensional (3D) Video-assisted telescope operating monitor (VITOM) or exoscope. OBJECTIVES: To assess the role and potential advantages of exoscope in the minimally invasive surgery of traumatic thoracolumbar spinal cord compression comparing traditional magnification systems. SETTING: The study was conducted in a Northern Italy Spinal Trauma Center. METHODS: We reported 10 consecutive thoracolumbar (T11-L2) burst fractures associated with spinal cord compression treated with minimally invasive corpectomy and exoscope-assisted spinal decompression. Three main indicators were retrospectively analyzed: surgical time, blood loss, and intraoperative complications. The data were compared with those obtained from an equal sample of 10 procedures performed by the same surgeon with the same technique, but traditional microscope assisted. User impressions in terms of ergonomics, magnification, and image quality were rated differently. RESULTS: A small reduction of surgical time and blood loss were observed in the exoscope assisted group. There were no intraoperative complications attributed to visualization mode or conversion to the traditional microscope in any procedure. In our experience the exoscope allowed a better magnification and image definition with better ergonomics and user-friendliness. CONCLUSIONS: In our preliminary experience the exoscope new technology is a safe and effective tool for spinal cord minimally invasive decompression in thoracolumbar burst fractures. The stereoscopic vision provided by 3D images seems to be crucial in hand eye coordination. There are clear advantages in terms of maneuverability, wide field of view, deep focus, and more comfortable posture for the spinal surgeon.

Consensus for management of sacral fractures: from the diagnosis to the treatment, with a focus on the role of decompression in sacral fractures.

BACKGROUND: There is no evidence in the current literature about the best treatment option in sacral fracture with or without neurological impairment. MATERIALS AND METHODS: The Italian Pelvic Trauma Association (A.I.P.) decided to organize a consensus to define the best treatment for traumatic and insufficiency fractures according to neurological impairment. RESULTS: Consensus has been reached for the following statements: When complete neurological examination cannot be performed, pelvic X-rays, CT scan, hip and pelvis MRI, lumbosacral MRI, and lower extremities evoked potentials are useful. Lower extremities EMG should not be used in an acute setting; a patient with cauda equina syndrome associated with a sacral fracture represents an absolute indication for sacral reduction and the correct timing for reduction is "as early as possible". An isolated and incomplete radicular neurological deficit of the lower limbs does not represent an indication for laminectomy after reduction in the case of a displaced sacral fracture in a high-energy trauma, while a worsening and progressive radicular neurological deficit represents an indication. In the case of a displaced sacral fracture and neurological deficit with imaging showing no evidence of nerve root compression, a laminectomy after reduction is not indicated. In a patient who was not initially investigated from a neurological point of view, if a clinical investigation conducted after 72 h identifies a neurological deficit in the presence of a displaced sacral fracture with nerve compression on MRI, a laminectomy after reduction may be indicated. In the case of an indication to perform a sacral decompression, a first attempt with closed reduction through external manoeuvres is not mandatory. Transcondylar traction does not represent a valid method for performing a closed decompression. Following a sacral decompression, a sacral fixation (e.g. sacroiliac screw, triangular osteosynthesis, lumbopelvic fixation) should be performed. An isolated and complete radicular neurological deficit of the lower limbs represents an indication for laminectomy after reduction in the case of a displaced sacral fracture in a low-energy trauma associated with imaging suggestive of root compression. An isolated and incomplete radicular neurological deficit of the lower limbs does not represent an absolute indication. A worsening and progressive radicular neurological deficit of the lower limbs represents an indication for laminectomy after reduction in the case of a displaced sacral fracture in a low-energy trauma associated with imaging suggestive of root compression. In the case of a displaced sacral fracture and neurological deficit in a low-energy trauma, sacral decompression followed by surgical fixation is indicated. CONCLUSIONS: This consensus collects expert opinion about this topic and may guide the surgeon in choosing the best treatment for these patients. LEVEL OF EVIDENCE: IV. TRIAL REGISTRATION: not applicable (consensus paper).

RNA-Binding Proteins as Epigenetic Regulators of Brain Functions and Their Involvement in Neurodegeneration.

A central aspect of nervous system development and function is the post-transcriptional regulation of mRNA fate, which implies time- and site-dependent translation, in response to cues originating from cell-to-cell crosstalk. Such events are fundamental for the establishment of brain cell asymmetry, as well as of long-lasting modifications of synapses (long-term potentiation: LTP), responsible for learning, memory, and higher cognitive functions. Post-transcriptional regulation is in turn dependent on RNA-binding proteins that, by recognizing and binding brief RNA sequences, base modifications, or secondary/tertiary structures, are able to control maturation, localization, stability, and translation of the transcripts. Notably, most RBPs contain intrinsically disordered regions (IDRs) that are thought to be involved in the formation of membrane-less structures, probably due to liquid-liquid phase separation (LLPS). Such structures are evidenced as a variety of granules that contain proteins and different classes of RNAs. The other side of the peculiar properties of IDRs is, however, that, under altered cellular conditions, they are also prone to form aggregates, as observed in neurodegeneration. Interestingly, RBPs, as part of both normal and aggregated complexes, are also able to enter extracellular vesicles (EVs), and in doing so, they can also reach cells other than those that produced them.

Artificial Intelligence Accurately Detects Traumatic Thoracolumbar Fractures on Sagittal Radiographs.

Background and Objectives: Commonly being the first step in trauma routine imaging, up to 67% fractures are missed on plain radiographs of the thoracolumbar (TL) spine. The aim of this study was to develop a deep learning model that detects traumatic fractures on sagittal radiographs of the TL spine. Identifying vertebral fractures in simple radiographic projections would have a significant clinical and financial impact, especially for low- and middle-income countries where computed tomography (CT) and magnetic resonance imaging (MRI) are not readily available and could help select patients that need second level imaging, thus improving the cost-effectiveness. Materials and Methods: Imaging studies (radiographs, CT, and/or MRI) of 151 patients were used. An expert group of three spinal surgeons reviewed all available images to confirm presence and type of fractures. In total, 630 single vertebra images were extracted from the sagittal radiographs of the 151 patients-302 exhibiting a vertebral body fracture, and 328 exhibiting no fracture. Following augmentation, these single vertebra images were used to train, validate, and comparatively test two deep learning convolutional neural network models, namely ResNet18 and VGG16. A heatmap analysis was then conducted to better understand the predictions of each model. Results: ResNet18 demonstrated a better performance, achieving higher sensitivity (91%), specificity (89%), and accuracy (88%) compared to VGG16 (90%, 83%, 86%). In 81% of the cases, the "warm zone" in the heatmaps correlated with the findings, suggestive of fracture within the vertebral body seen in the imaging studies. Vertebras T12 to L2 were the most frequently involved, accounting for 48% of the fractures. A4, A3, and A1 were the most frequent fracture types according to the AO Spine Classification. Conclusions: ResNet18 could accurately identify the traumatic vertebral fractures on the TL sagittal radiographs. In most cases, the model based its prediction on the same areas that human expert classifiers used to determine the presence of a fracture.

Surgical pathway proposal for severe paralytic scoliosis in adolescents with myelomeningocele.

PURPOSE: The increased life expectancy of patients with myelomeningocele led to the necessity of new management for addressing complex spine deformities with severe pelvic obliquity. Tethered cord release (TCR) and spinal fusion were described as treatment options. However, nowadays, the surgical strategy is not well defined and high rates of mechanical failures and complications are reported. Our aim was to propose a new two-stage surgical pathway to treat a selected group of severe myelomeningocele scoliosis. METHODS: This is a retrospective series of myelomeningocele scoliosis in paralytic adolescent patients treated with concurrent TCR and posterior spinal fusion (PSF), followed by delayed anterior fusion (ASF) through minimally invasive lateral approach. Inclusion criteria were as follows: evolutive scoliosis in tethered cord syndrome and paraplegia, main curve >70°, pelvic obliquity >20°, and age between 10 and 18 years. Clinical, surgical, and radiographic parameters were evaluated preoperatively and at a mean follow-up (FU) of 2.8 years. RESULTS: Six patients out of 58 met the inclusion criteria and were included in the study (mean age 12.3 years old). The mean curve and pelvic obliquity correction were 68.8% and 82%, respectively. No loss of correction was recorded at FU. One case of cerebrospinal fluid leakage requiring revision surgery was recorded. CONCLUSION: To the best of our knowledge, this is the first study proposing a two-stage surgical pathway for severe MMC spinopelvic deformity treatment. Concurrent TCR and PSF with delayed minimally invasive ASF permitted to minimize complications providing good fusion rates without loss of correction and implant failure.

Primary amputation vs limb salvage in mangled extremity: a systematic review of the current scoring system.

BACKGROUND: In the last decades a lot of new reconstructive techniques were developed for the treatment of mangled lower extremity. However failed attempt to limb salvage is related to high risk of mortality for the patient. Several scores were developed to establish guidelines for the decision to amputate or not, however in literature there is no consensus about the reliability of this scores. METHODS: The authors focused their attention on the most used score system to provide guidance of the management of a mangled lower limb. The search term used included mangled lower extremity, MESS, PSI, LSI and NISSSA. The inclusion criteria were: studies dealing with mangled lower extremity; articles reporting MESS, PSI, LSI or NISSSA scores; articles published in English in PubMed, Cochrane, Scopus and web of science in the last 30 years, minimum number of cases in study of 15, minimum follow up of 1 year. RESULTS: According with the criteria described above, we found 134 articles in PubMed, 165 articles in Scopus, 111 articles in the Cochrane Library and 108 articles in Web of Science. The most used score in literature is the MESS. Few results are shown using the other severity scores. There are a lot of controversies in literature about the use of this scale. MESS seems to be more accurate than the LSI in prediction of limb salvage. LSI score shows better results when applied to type III tibial fractures. High sentivity of the PSI score is described when applied to predict successful limb salvage. Low sensitivity and specificity are described for the NISSSA score. The literature is very poor of articles related to mangled lower extremity in children. Higher sensitivity and specificity are described for these scores in children when compared to adult population. CONCLUSION: The mangled lower extremity treatment is a challenge for the surgeon. Many scores were developed to help the surgeon, however they cannot be used as the sole criterion by which amputation decision are made and, in case of succesful limb salvage, they are not predictive of the functional recovery. Moreover, undue enthusiasm for new surgical techniques can lead to increased morbidity and mortality in case of secondary amputation.

The pharmacological management of myelin oligodendrocyte glycoprotein-immunoglobulin G associated disease (MOGAD): an update of the literature.

INTRODUCTION: Myelin oligodendrocyte glycoprotein-immunoglobulin G associated disease (MOGAD) is a clinical entity distinct from multiple sclerosis and aquaporin-4 (AQP4+)-IgG-positive neuromyelitis optica spectrum disorder. There is a lack of evidence regarding the efficacy and safety of current treatments used for MOGAD. AREAS COVERED: In this article, the authors review the currently available literature on the pharmacological management of MOGAD. This article is based on an extensive search for articles including meta-analyses, clinical trials, systematic reviews, observational studies, case series and case reports. EXPERT OPINION: Intravenous high-dose methylprednisolone is the most common therapy for acute attack with patients having a good treatment response. In cases with poor recovery, intravenous immunoglobulins (IVIG) or plasma-exchange proved to be effective. Maintenance therapies include mycophenolate mofetil, azathioprine, IVIG, oral corticosteroids, rituximab, and interleukin-6 receptor (IL6-R) antagonists. Rituximab is the most used drug while IL6-R antagonists emerged as an effective option for people not responding to current treatments. Larger prospective studies with longer follow-ups are needed to confirm whether the blockage of the IL6-R is an effective and safe option. Since there is no evidence of major safety issues related to the new available therapies, the authors believe that waiting for disease activity to consider a possible treatment change, is an unwise approach.

Role of Post-Transcriptional Regulation in Learning and Memory in Mammals.

After many decades, during which most molecular studies on the regulation of gene expression focused on transcriptional events, it was realized that post-transcriptional control was equally important in order to determine where and when specific proteins were to be synthesized. Translational regulation is of the most importance in the brain, where all the steps of mRNA maturation, transport to different regions of the cells and actual expression, in response to specific signals, constitute the molecular basis for neuronal plasticity and, as a consequence, for structural stabilization/modification of synapses; notably, these latter events are fundamental for the highest brain functions, such as learning and memory, and are characterized by long-term potentiation (LTP) of specific synapses. Here, we will discuss the molecular bases of these fundamental events by considering both the role of RNA-binding proteins (RBPs) and the effects of non-coding RNAs involved in controlling splicing, editing, stability and translation of mRNAs. Importantly, it has also been found that dysregulation of mRNA metabolism/localization is involved in many pathological conditions, arising either during brain development or in the adult nervous system.

Involvement of Astrocytes in the Formation, Maintenance, and Function of the Blood-Brain Barrier.

The blood-brain barrier (BBB) is a fundamental structure that protects the composition of the brain by determining which ions, metabolites, and nutrients are allowed to enter the brain from the blood or to leave it towards the circulation. The BBB is structurally composed of a layer of brain capillary endothelial cells (BCECs) bound to each other through tight junctions (TJs). However, its development as well as maintenance and properties are controlled by the other brain cells that contact the BCECs: pericytes, glial cells, and even neurons themselves. Astrocytes seem, in particular, to have a very important role in determining and controlling most properties of the BBB. Here, we will focus on these latter cells, since the comprehension of their roles in brain physiology has been continuously expanding, even including the ability to participate in neurotransmission and in complex functions such as learning and memory. Accordingly, pathological conditions that alter astrocytic functions can alter the BBB's integrity, thus compromising many brain activities. In this review, we will also refer to different kinds of in vitro BBB models used to study the BBB's properties, evidencing its modifications under pathological conditions.

Efficacy and Safety of Rescue Treatment with Plasma Exchange in Patients with Acute Inflammatory Neurological Disorders: A Single Center Experience.

BACKGROUND: Therapeutic plasma exchange (TPE) is a highly effective rescue treatment for patients with acute exacerbation of neuroimmunological disease that removes circulating autoantibodies and inflammatory components from the bloodstream. The aims of this study are to explore the safety and the effectiveness of TPE in patients with autoimmune neurological disorders. METHODS: We retrospectively evaluated the frequency of adverse events (AEs) and the effectiveness of TPE using the modified Ranking Scale (mRS) in patients with acute neurological flares who underwent TPE at the University Hospital of Palermo. RESULTS: Of 59 patients, the majority underwent TPE due to multiple sclerosis (MS) relapse. In 23.7% of cases, TPE was performed before obtaining a definite diagnosis due to the severity of the clinical presentation. After TPE, the mRS score was globally reduced (p < 0.0001), and this effect was marked in patients with MS, Guillain-Barré syndrome, and myasthenia gravis crisis but not in those with paraneoplastic syndromes. Circulating pathogenetic antibodies, younger age, and the early use of TPE were factors strongly associated with TPE effectiveness. The overall safety profile of TPE was satisfactory with an AE frequency of 15%. CONCLUSIONS: These results highlight the early use of TPE in patients with circulating pathogenetic antibodies as well as its favorable safety profile.

Implementation of Robotic Exoscope in Minimally Invasive Corpectomy at Thoracolumbar Junction for the Treatment of Traumatic Spinal Cord Compression.

The development and diffusion of minimally invasive (MI) approaches have coincided with improvements in magnification systems. The exoscope will probably open a new era in new technologies in spinal surgery. This study reports a retrospective series of 19 thoracolumbar (T11-L2) burst fractures with anterior column failure and cord compression, treated with MI corpectomy and spinal decompression assisted by a three-dimensional high-definition exoscope (Video 1). Exclusion criteria were pathologic or osteoporotic fractures, multilevel fractures, and previous surgery at the site of the fracture. Three key indicators were recorded: surgical time, blood loss, and intraoperative complications. A questionnaire was administered to assess the users' exoscope experience with ergonomics, preparation, magnification, image definition, illumination, and user-friendliness, compared with the operative microscope. To the best of our knowledge, this is the first study reporting on exoscope-assisted MI corpectomy. This procedure permitted low blood loss and less surgical time without intraoperative complications. The exoscope offers clear advantages in terms of ergonomics, definition, and user-friendliness. Moreover, it is a suitable instrument for training and education, providing an opportunity for better interaction with other members of the surgical staff.

High-intensity interval training improves bone remodeling, lipid profile, and physical function in multiple sclerosis patients.

Multiple sclerosis (MS) is a demyelinating and neurodegenerative disease due to an autoimmune chronic inflammatory response, yet the etiology is currently not completely understood. It is already known that physical activity plays an essential role in improving quality of life, especially in neuropathological conditions. The study was aimed to investigate the possible benefits of high-intensity interval training (HIIT) in bone and lipid metabolism markers, and neuromotor abilities in MS patients. 130 participants were recruited; 16 subjects with MS met the inclusion criteria and were included in the data analysis. The patients were randomly assigned to two groups: a Control group (CG) (34.88 ± 4.45 yrs) that didn't perform any physical activity and the Exercise group (EG) (36.20 ± 7.80 yrs) that performed HIIT protocol. The training program was conducted remotely by a kinesiologist. It was performed three times a week for 8 weeks. At the beginning (T0) and the end of the study (T1) physical function tests, bone remodelling markers, and lipid markers analyses were performed. After 8 weeks of training the wall squat (s) (T0 = 27.18 ± 4.21; T1 = 41.68 ± 5.38, p ≤ 0.01) and Time Up and Go test (s) (T0 = 7.65 ± 0.43; T1 = 6.34 ± 0.38 p ≤ 0.01) performances improved; lipid markers analysis showed a decrease in Total (mg/dl) (T0 = 187.22 ± 15.73; T1 = 173.44 ± 13.03, p ≤ 0.05) and LDL (mg/dl) (T0 = 108 ± 21.08; T1 = 95.02 ± 17.99, p < 0.05) cholesterol levels. Additionally, the levels of osteocalcin (µg/L), a marker of bone formation increased (T0 = 20.88 ± 4.22; T1 = 23.66 ± 6.24, p < 0.05), 25-OH Vitamin D (µg/L) improved after 8 weeks (T0 = 21.11 ± 7.11; T1 = 27.66 ± 7.59, p < 0.05). HIIT had an effect on lower limb strength and gait control, improved bone formation, and lipid management, in MS patients.

The Role of Human Microbiota in Myasthenia Gravis: A Narrative Review.

Myasthenia gravis (MG) is an autoimmune neuromuscular disease characterized by fluctuating weakness of the skeletal muscles. Although antibodies against the neuromuscular junction components are recognized, the MG pathogenesis remains unclear, even if with a well-known multifactorial character. However, the perturbations of human microbiota have been recently suggested to contribute to MG pathogenesis and clinical course. Accordingly, some products derived from commensal flora have been demonstrated to have anti-inflammatory effects, while other have been shown to possess pro-inflammatory properties. In addition, patients with MG when compared with age-matched controls showed a distinctive composition in the oral and gut microbiota, with a typical increase in Streptococcus and Bacteroides and a reduction in Clostridia as well as short-chain fatty acid reduction. Moreover, restoring the gut microbiota perturbation has been evidenced after the administration of probiotics followed by an improvement of symptoms in MG cases. To highlight the role of the oral and gut microbiota in MG pathogenesis and clinical course, here, the current evidence has been summarized and reviewed.

Sex differences in neuromuscular disorders.

The prevalence, onset, pathophysiology, and clinical course of many neuromuscular disorders (NMDs) may significantly differ between males and females. Some NMDs are more frequently observed in females, and characterized to show a higher grade of severity during or after the pregnancy. Meanwhile, others tend to have an earlier onset in males and exhibit a more variable progression. Prevalently, sex differences in NMDs have a familiar character given from genetic inheritance. However, they may also influence clinical presentation and disease severity of acquired NMD forms, and are represented by both hormonal and genetic factors. Consequently, to shed light on the distinctive role of biological factors in the different clinical phenotypes, we summarize in this review the sex related differences and their distinctive biological roles emerging from the current literature in both acquired and inherited NMDs.

Frequency and Correlates of Mild Cognitive Impairment in Myasthenia Gravis.

BACKGROUND: Antibodies against acetylcholine receptors (AChRs) can also target nicotinic AChRs that are present throughout the central nervous system, thus leading to cognitive dysfunctions in patients with myasthenia gravis (MG). However, the presence of cognitive impairment in MG is controversial, and the factors that may influence this risk are almost completely unknown. In this study, the frequency of mild cognitive impairment (MCI) in MG, as well as the clinical, immunological, and behavioral correlates of MCI in MG were evaluated. METHODS: A total of 52 patients with MG underwent a comprehensive assessment including motor and functional scales, serological testing, and neuropsychological and behavioral evaluation. RESULTS: The frequency of MCI was 53.8%, and the most impaired cognitive domains were, in order, visuoconstructive/visuospatial skills, memory, and attention. After multivariate analysis, only pyridostigmine use was inversely associated with the presence of MCI, while a trend toward a positive association between MCI and disease severity and arms/legs hyposthenia was found. Correlation analyses showed that daily doses of prednisone and azathioprine significantly correlated with depressive symptomatology, while disease severity significantly correlated with depressive symptomatology and sleep disturbance. CONCLUSIONS: The presence of MCI is rather frequent in MG and is characterized by multidomain amnestic impairment. Such preliminary data need further confirmation on larger case series.

Spinal injury in major trauma: Epidemiology of 1104 cases from an Italian first level trauma center.

INTRODUCTION: Traumatic spinal injuries are frequent and their management is debated, especially in major trauma patients. This study aims to describe a large population of major trauma patients with vertebral fractures to improve prevention measures and fracture management. PATIENTS AND METHODS: Retrospective analysis of 6274 trauma patients prospectively collected between October 2010 and October 2020. Collected data include demographics, mechanism of trauma, type of imaging, fracture morphology, associated injuries, injury severity score (ISS), survival, and death timing. The statistical analysis focused on mechanism of trauma and the search of predictive factors for critical fractures. RESULTS: Patients showed a mean age of 47 years and 72.5% were males. Trauma included 59.9% of road accidents and 35.1% of falls. 30.7% patients had at least a severe fracture, while 17.2% had fractures in multiple spinal regions. 13.7% fractures were complicated by spinal cord injury (SCI). The mean ISS of the total population was 26.4 (SD 16.3), with 70.7% patients having an ISS≥16. There is a higher rate of severe fractures in fall cases (40.1%) compared to RA (21.9% to 26.3%). The probability of a severe fracture increased by 164% in the case of fall and by 77% in presence of AIS≥3 associated injury of head/neck while reduced by 34% in presence of extremities associated injuries. Multiple level injuries increased with ISS rise and in the case of extremities associated injuries. The probability of a severe upper cervical fracture increased by 5.95 times in the presence of facial associated injuries. The mean length of stay was 24.7 days and 9.6% of patients died. CONCLUSIONS: In Italy, road accidents are still the most frequent trauma mechanism and cause more cervico-thoracic fractures, while falls cause more lumbar fractures. Spinal cord injuries represent an indicator of more severe trauma. In motorcyclists or fallers/jumpers, there is a higher risk of severe fractures. When a spinal injury is diagnosed, the probability of a second vertebral fracture is consistent. These data could help the decisional workflow in the management of major trauma patients with vertebral injury.

Evaluation of serum and cerebrospinal fluid biomarkers after vaccination against SARS-CoV-2.

OBJECTIVE: Vaccines are a major achievement of science, and new vaccines against SARS-CoV-2 are protecting the entire population from a life-threatening infection. Although several neurological complications or worsening of pre-existing neurological conditions after vaccination have been observed, whether a biological plausibility exist between new vaccines against-SARS-CoV-2 and neurological consequences is unclear. The aim of this study is to evaluate whether vaccines against SARS-CoV-2 induce systemic or cerebrospinal fluid alterations in patients with neurological disorders. METHODS: Patients who underwent lumbar puncture (LP) between February 2021 and October 2022 were enrolled. Serum C-reactive protein (CRP), neutrophil to lymphocyte ratio (NLR), cerebrospinal fluid total protein content (CSF-TPc), glucose CSF/serum ratio, number of CSF cells per cubic millimeter, and CSF neurofilament light chain (CSF-NfL) were compared between unvaccinated and vaccinated patients. RESULTS: A total of 110 patients were included and fitted into three groups according firstly to vaccination status (vaccinated and unvaccinated) and then to time from last dose of vaccine to LP (within or after 3 months). TPc, CSF/SGlu ratio, number of cells per cubic millimeter, CSF-NfL, CRP, and NLR were not different between groups (all p > 0.05), and also, they did not differ neither according to age nor diagnosis. No relevant differences between groups were also noticed when the at-risk time window was set to 6 weeks. INTERPRETATION: No signs of neuroinflammation, axonal loss and systemic inflammation were found in patients with neurological disorders after anti-SARS-CoV-2 vaccination compared with unvaccinated ones.