Primary intracranial sarcomas of the central nervous system are rare tumors. They mainly arise from intracranial mesenchymal tissue present in the meninges and can occur at any age. Sometimes ...osteosarcoma can involve the skull rather than long body bones. In this latter case it is the more common subtype. Surgery, when possible, is a mandatory option often associated with radiation therapy (RT) and chemotherapy. Brain radionecrosis (BRN) is commonly observed due to the growing use of radiosurgery and higher cumulative doses of radiation therapy. The combination of perfusion magnetic resonance imaging and 18fluoro-deoxy-glucose positron emission tomography can help to differentiate tumor progression from radiation injury. Steroids, anticoagulants, and bevacizumab usually control BRN. However, BRN can also have an unfavorable course.
Here, we present a case of a 60-year-old male who underwent surgery for a brain tumor. The examination showed a primary undifferentiated high-grade sarcoma. Adjuvant RT was given with a total dose of 60 Gy. Six months later, the patient underwent a second surgery that revealed a BRN progressing despite different pharmacologic attempts.
Primary intracranial sarcomas of the central nervous system are less prevalent among older adults with respect to the younger population. The use of RT alone or combined with chemotherapy is aimed at prolonging survival. However, it is not clearly defined if adjuvant treatments affect this parameter in older patients. RT should be carefully discussed owing to its potential severe neurologic toxicity. Indeed, a BRN can have a significant impact on quality of life and lead to death in certain cases.
Metabolic reprogramming is shaped to support specific cell functions since cellular metabolism controls the final outcome of immune response. Multiple sclerosis (MS) is an autoimmune disease ...resulting from loss of immune tolerance against central nervous system (CNS) myelin. Metabolic alterations of T cells occurring during MS are not yet well understood and their studies could have relevance in the comprehension of the pathogenetic events leading to loss of immune tolerance to self and to develop novel therapeutic strategies aimed at limiting MS progression.
In this report, we observed that extracellular acidification rate (ECAR) and oxygen consumption rate (OCR), indicators of glycolysis and oxidative phosphorylation, respectively, were impaired during T cell activation in naïve-to-treatment relapsing remitting (RR)MS patients when compared with healthy controls. These results were also corroborated at biochemical level by a reduced expression of the glycolitic enzymes aldolase, enolase 1, hexokinase I, and by reduction of Krebs cycle enzymes dihydrolipoamide-S-acetyl transferase (DLAT) and dihydrolipoamide-S-succinyl transferase (DLST). Treatment of RRMS patients with interferon beta-1a (IFN beta-1a) was able to restore T cell glycolysis and mitochondrial respiration as well as the amount of the metabolic enzymes to a level comparable to that of healthy controls. These changes associated with an up-regulation of the glucose transporter-1 (GLUT-1), a key element in intracellular transport of glucose.
Our data suggest that T cells from RRMS patients display a reduced engagement of glycolysis and mitochondrial respiration, reversible upon IFN beta-1a treatment, thus suggesting an involvement of an altered metabolism in the pathogenesis of MS.
Background and purpose
Longitudinally extensive transverse myelitis (LETM) associated with aquaporin‐4 autoantibodies (AQP4‐IgG) can cause severe disability. Early diagnosis and prompt treatment are ...critical to prevent relapses. A novel score is described based on clinical and neuroimaging characteristics that predicts AQP4‐IgG positivity in patients with LETM.
Methods
Patients were enrolled both retrospectively and prospectively from multiple Italian centers. Clinical and neuroimaging characteristics of AQP4‐IgG positive and negative patients were compared through univariate and multivariate analysis.
Results
Sixty‐six patients were included. Twenty‐seven (41%) were AQP4‐IgG positive and median age at onset was 45.5 years (range 19–81, interquartile range 24). Female sex (odds ratio OR 17.9, 95% confidence interval CI 2.6–381.9; p = 0.014), tonic spasms (OR 45.6, 95% CI 3.1–2197; p = 0.017) and lesion hypointensity on T1‐weighted images (OR 52.9, 95% CI 6.8–1375; p = 0.002) were independently associated with AQP4‐IgG positivity. The AQP4‐IgG positivity in myelitis (AIM) score predicted AQP4‐IgG positivity with 85% sensitivity and 95% specificity. Positive and negative likelihood ratios were 16.6 and 0.2 respectively. The inter‐rater and intra‐rater agreement in the score application were both excellent.
Conclusions
The AIM score predicts AQP4‐IgG positivity with good sensitivity and specificity in patients with a first episode of LETM. The score may assist clinicians in early diagnosis and treatment of AQP4‐IgG positive LETM.
In this multicenter study, a score is developed to predict aquaporin‐4 (AQP4) immunoglobulin G (IgG) positivity in patients with longitudinally extensive myelitis (LETM). The AQP‐4‐IgG positive myelitis (AIM) score was applied both retrospectively and prospectively for 66 LETM patients, and a score ≥5 predicted AQP4‐IgG positivity with 85% sensitivity and 95% specificity. The AIM score appears a reliable tool to aid in the early diagnosis and treatment of AQP4‐IgG positive LETM.
To minimize the risk of Progressive Multifocal Leukoencephalopathy and rebound in JCV-positive multiple sclerosis (MS) patients after 24 natalizumab doses, it has been proposed to extend the ...administrations interval. The objective is to evaluate the EID efficacy on MRI activity compared with the standard interval dosing (SID).
Observational, multicentre, retrospective cohort study, starting from the 24th natalizumab infusion to the loss of follow-up or 2 years after baseline. Three hundred and sixteen patients were enrolled. The median dose interval (MDI) following the 24th infusion was 5 weeks, with a bimodal distribution (modes at 4 and 6 weeks). Patients were grouped into 2 categories according to the mean number of weeks between doses: <5 weeks, SID; ≥5 weeks, EID.
One hundred and eighty-seven patients were in the SID group (MDI = 4.5 weeks) and 129 in the EID group (MDI 6.1 weeks). The risk to develop active lesions on MRI is similar in SID and EID groups during the 6 and 12 months after the 24th natalizumab infusion, respectively 4.27% (95% CI:0.84–7.70) vs 4.71% (95% CI:0.16–9.25%) p = 0.89 and 8.50% (95% CI:4.05–12.95) vs 6.55% (95% CI:2.11–11.00%) p = 0.56. The EID regimen does not appear to increase the occurrence of MRI activity during follow-up.
There is no evidence of the reduced efficacy of natalizumab in an EID setting regarding the MRI activity. This observation supports the need for a bigger randomized study to assess the need to change the standard of the natalizumab dosing schedule, to better manage JCV-positive patients.
Display omitted
•Extending the natalizumab interval dose over 4 weeks could reduce Progressive Multifocal Leukoencephalopathy risk.•Extending the administrations interval of natalizumab could increase MRI activity.•In our observational, multicentre, retrospective cohort study over 316 patients with multiple sclerosis, showed that the extended dose regimen does not increase the occurrence of MRI activity after 6 and 12 months.•The extended dose natalizumab regimen could maintain the natalizumab efficacy and could be a useful dosing schedule in JCV-positive patients.
Epigenetics connects genetic and environmental factors: it includes DNA methylation, histone post‐translational modifications and the regulation of chromatin accessibility by non‐coding RNAs, all of ...which control constitutive or inducible gene transcription. This plays a key role in harnessing the transcriptional programs of both innate and adaptive immune cells due to its plasticity and environmental‐driven nature, piloting myeloid and lymphoid cell fate decisions with no change in their genomic sequence. In particular, epigenetic marks at the site of lineage‐specific transcription factors and maintenance of cell type‐specific epigenetic modifications, referred to as ‘epigenetic memory’, dictate cell differentiation, cytokine production and functional capacity following repeated antigenic exposure in memory T cells. Moreover, metabolic and epigenetic reprogramming occurring during a primary innate immune response leads to enhanced responses to secondary challenges, a phenomenon known as ‘trained immunity’. Here, we discuss how stable and dynamic epigenetic states control immune cell identity and plasticity in physiological and pathological conditions. Dissecting the regulatory circuits of cell fate determination and maintenance is of paramount importance for understanding the delicate balance between immune cell activation and tolerance, in healthy conditions and in autoimmune diseases.
External cues (e.g., environment, diet) and age converge on epigenetics that affects gene expression through specific DNA and histone modifications or non‐coding RNAs; this, together with genetic factors, tailors immune cell function. Through complex interactions with transcription factor networks and other transcriptional machinery, epigenetic modifications support the functional exchange between repressed and active states of chromatin to prime immune activation, transcriptional memory, innate immune training and tolerance.
To analyse autoantibody status in a well-defined European multicentre cohort of patients with epilepsy of unknown aetiology and to validate the recently proposed Antibody Prevalence in Epilepsy ...(APE2) and Response to ImmunoTherapy in Epilepsy (RITE2) scores.
We retrospectively collected clinical and paraclinical data of 92 patients referred to the Neurology Units of Verona and Salzburg between January 2014 and July 2019 with new-onset epilepsy, status epilepticus or chronic epilepsy of unknown aetiology. Fixed and live cell-based assays, tissue-based assays, immunoblot, and live rat hippocampal cell cultures were performed in paired serum/cerebrospinal fluid (CSF) to detect antineuronal and antiglial antibodies. The APE2 and RITE2 scores were then calculated and compared with clinical and laboratory data.
Autoantibodies were detected in 29/92 patients (31.5%), with multiple positivity observed in 6/29 cases. The APE2 score (median 5, range 1-15) significantly correlated with antibody positivity (p=0.014), especially for the presence of neuropsychiatric symptoms (p<0.01), movement disorders (p<0.01), dysautonomia (p=0.03), faciobrachial dyskinesias (p=0.03) and cancer history (p<0.01). Status epilepticus was significantly more frequent in antibody-negative patients (p<0.01). Among the items of the RITE2 score, early initiation of immunotherapy correlated with a good treatment response (p=0.001), whereas a cancer history was significantly more common among non-responders (p<0.01). Persistence of neuropsychiatric symptoms and seizures correlated with antiepileptic maintenance after at least 1 year.
This is the first study that independently validates the APE2 and RITE2 scores and includes the largest cohort of patients whose paired serum and CSF samples have been tested for autoantibodies possibly associated with autoimmune epilepsy.
Background
COVID-19 vaccines have been recommended to people with multiple sclerosis (pwMS) and, to ensure durable immunity, a third booster dose has been administered in several countries. Data ...about potential risks associated with the third booster dose in pwMS, such as vaccine-triggered disease exacerbations, are still scarce.
Objective
To investigate whether the administration of a third booster dose of mRNA COVID-19 vaccines was associated with an increased risk of short-term disease reactivation in a large cohort of pwMS.
Methods
We retrospectively selected 1265 pwMS who received a third booster dose of an mRNA COVID-19 vaccine. Demographic and clinical data were collected, including the presence, number and characteristics of relapses in the 60 days prior to and after the third booster dose.
Results
In the selected cohort, the relapse rate in the two months after administration of the third booster dose of mRNA COVID-19 vaccines did not increase when compared with the prior two months. Indeed, the percentage of pwMS experiencing relapses in the 60 days following the administration of the third booster dose was 2.1%, similar to the percentage recorded in 60 days prior to vaccination, which was 1.9%.
Conclusions
The third booster dose of mRNA COVID-19 vaccines appeared to be safe for pwMS.
PDF
