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Glioblastoma (GBM) has an increasing incidence and dismal prognosis in older adults. This study evaluated neurocognitive status of an older adult population with GBM and its correlation with clinical and demographical variables.Each patient underwent an extended neuropsychological evaluation by means of a battery of standardized tests describing eight cognitive domains: global function; verbal learning; short- and long-term memory (LTM); executive functions (EFs); abstract reasoning (AR); attention; and visuo-constructional abilities (CA).We assessed 79 patients with GBM (median age: 74 years). Out of this initial sample, a subgroup of seventeen patients with six-month median time underwent a follow-up test session. 46 out of the 79 patients (58.2%) presented multi-domain cognitive impairment, 24 patients (30.3%) showed single-domain cognitive impairment and only seven (9%) showed no cognitive impairment. Kaplan Meier estimator showed that patients with AR deficit had a poorer prognosis in terms of progression-free survival and overall survival (p .001). At the multivariate analysis AR (deficit vs non; hazard ratio (HR) = 5.07, 95%; confidence interval (CI): 1.91-13.46; p .001) was correlated with disease progression and overall survival, AR (deficit vs non; HR = 7.24, 95% CI: 2.58-20.32; p .001). Eight out of seventeen patients who underwent follow-up test session showed cognitive improvement, five resulted in further deterioration, and four patients remained stable. LTM, EF, and CA were the most affected functions at follow-up, while verbal learning was the most improved one in patients with cognitive improvement.Cognitive functioning evaluation should be included among the standard clinical endpoints in the treatment of older adult neuro-oncology patients.

Bevacizumab is an anti-angiogenic monoclonal antibody targeting Vascular Endothelial Growth Factor (VEGF) that induces the proliferation and migration of vascular endothelial cells thus, promoting vasculogenesis. Bevacizumab inhibits cancer angiogenesis, which is fundamental for either tumor development, exponential growth, or metastatic spread by supplying nutrients and oxygen. We report a new possible adverse event of bevacizumab, a Cerebral Amyloid Angiopathy-Related Inflammation (CAARI), in a 72-year-old woman with metastatic cervical cancer. After six cycles every three weeks of chemotherapy (cisplatin, paclitaxel, bevacizumab) and following two maintenance bevacizumab administrations, the patient presented a worsening confusional state. The MRI scan showed bilateral asymmetric temporo-parieto-occipital hyperintensity with numerous cortical microbleeds indicative of a CAARI. After stopping bevacizumab treatment, steroid therapy was administered resulting in rapid clinical improvement. The subsequent neurological and oncological follow-up was negative for recurrence. The patient was a heterozygote carrier for apolipoprotein-E ε4 that increases the risk of sporadic Cerebral Amyloid Angiopathy (CAA), which is characterized by beta-amyloid accumulation and fibrinoid necrosis in cerebral vasculature leading to micro/macrohemorrhages and dementia. Moreover, CAA is present in 30% of people aged over 60 years without dementia. In the brains of CAA patients, there is a proinflammatory state with cerebrovascular endothelial cell alteration and elevated levels of either adhesion molecules or inflammatory interleukins that increase the blood–brain barrier permeability. Moreover, CAARI is an inflammatory form of CAA. Inhibition of VEGF, which has anti-apoptotic, anti-inflammatory, and pro-survival effects on endothelial cells, impairs their regenerative capacity and increases expression of proinflammatory genes leading to weakened supporting layers of blood vessels and, hence, to damaged vascular integrity. In our patient, bevacizumab administration may have further increased permeability of cerebral microvasculature likely impaired by an underlying, asymptomatic CAA. To our knowledge, this is the first case reporting on the development of probable CAARI during bevacizumab treatment, which should alert the clinicians in case of neurological symptom onset in older patients under anti-angiogenic therapy.

Introduction Multiple sclerosis (MS) is a demyelinating disease of the central nervous system with an underlying immune-mediated and inflammatory pathogenesis. Innate immunity, in addition to the adaptive immune system, plays a relevant role in MS pathogenesis. It represents the immediate non-specific defense against infections through the intrinsic effector mechanism "immunothrombosis" linking inflammation and coagulation. Moreover, decreased cerebral blood volume (CBV), cerebral blood flow (CBF), and prolonged mean transit time (MTT) have been widely demonstrated by MRI in MS patients. We hypothesized that coagulation/complement and platelet activation during MS relapse, likely during viral infections, could be related to CBF decrease. Our specific aims are to evaluate whether there are differences in serum/plasma levels of coagulation/complement factors between relapsing-remitting (RR) MS patients (RRMS) in relapse and those in remission and healthy controls as well as to assess whether brain hemodynamic changes detected by MRI occur in relapse compared with remission. This will allow us to correlate coagulation status with perfusion and demographic/clinical features in MS patients. Materials and methods This is a multi-center, prospective, controlled study. RRMS patients (1° group: 30 patients in relapse; 2° group: 30 patients in remission) and age/sex-matched controls (3° group: 30 subjects) will be enrolled in the study. Patients and controls will be tested for either coagulation/complement (C3, C4, C4a, C9, PT, aPTT, fibrinogen, factor II, VIII, and X, D-dimer, antithrombin, protein C, protein S, von-Willebrand factor), soluble markers of endothelial damage (thrombomodulin, Endothelial Protein C Receptor), antiphospholipid antibodies, lupus anticoagulant, complete blood count, viral serological assays, or microRNA microarray. Patients will undergo dynamic susceptibility contrast-enhanced MRI using a 3.0-T scanner to evaluate CBF, CBV, MTT, lesion number, and volume. Statistical analysis ANOVA and unpaired t-tests will be used. The level of significance was set at p ≤ 0.05. Discussion Identifying a link between activation of coagulation/complement system and cerebral hypoperfusion could improve the identification of novel molecular and/or imaging biomarkers and targets, leading to the development of new effective therapeutic strategies in MS. Clinical trial registration Clinicaltrials.gov, identifier NCT04380220.

Infections are among the most frequent and challenging events in diabetic foot ulcers (DFUs). Pathogenic bacteria growing in biofilms within host tissue are highly tolerant to environmental and chemical agents, including antibiotics. The present study was aimed at assessing the use of silver sulfadiazine (SSD) for wound healing and infection control in 16 patients with DFUs harboring biofilm-growing Staphylococcus aureus and Pseudomonas aeruginosa. All patients received a treatment based on a dressing protocol including disinfection, cleansing, application of SSD, and application of nonadherent gauze, followed by sterile gauze and tibio-breech bandage, in preparation for toilet surgery after 30 days of treatment. Clinical parameters were analyzed by the T.I.M.E. classification system. In addition, the activity of SSD against biofilm-growing S. aureus and P. aeruginosa isolates was assessed in vitro. A total of 16 patients with S. aureus and P. aeruginosa infected DFUs were included in the study. Clinical data showed a statistically significant (p &lt, 0.002) improvement of patients&rsquo, DFUs after 30 days of treatment with SSD with significant amelioration of all the parameters analyzed. Notably, after 30 days of treatment, resolution of infection was observed in all DFUs. In vitro analysis showed that both S. aureus and P. aeruginosa isolates developed complex and highly structured biofilms. Antibiotic susceptibility profiles indicated that biofilm cultures were significantly (p &le, 0.002) more tolerant to all tested antimicrobials than their planktonic counterparts. However, SSD was found to be effective against fully developed biofilms of both S. aureus and P. aeruginosa at concentrations below those normally used in clinical preparations (10 mg/mL). These results strongly suggest that the topical administration of SSD may represent an effective alternative to conventional antibiotics for the successful treatment of DFUs infected by biofilm-growing S. aureus and P. aeruginosa.

Epilepsy occurs in 35-70% of patients with gliomas; glutamate plays a central role via AMPA-receptor activation, which is involved both in seizure activity and tumor growth. We conducted a retrospective study on brain tumor-related epilepsy patients (BTRE) treated with perampanel in add-on (PER) for 12 months, to evaluate efficacy and tollerability, according to real-life clinical practice.Medical records of eleven patients (9 males, mean age 54 years) with glioma and epilepsy treated with PER in add-on, for inadequate seizure control or adverse events (AEs) from previous antiepileptic drugs (AEDs) therapy, were reviewed. Data collected included: tumor history, molecular factors, systemic therapy, type and number of seizures and concomitant AEDs, and AEs.After 12 months of PER therapy, five patients were seizure-free, 4 had a seizure reduction ≥50% and the seizure frequency was unchanged in 2 patients. Responder rate was 81.8%. Two patients reported AEs; PER dose was reduced only in the one case. The final median dose of PER was 7.3 mg/day. We didn't find statistically significant differences in the comparison between mean values pre, mean values post and the average of decreasing number of seizures related to: histology, presence/absence of chemotherapy, radiotherapy, progression disease, KPS, IDH1, MGMT.Despite the limitations due to small number of patients in a retrospective study, the high rate of responder and seizure-free patients suggest that PER could be a therapeutic option in BTRE. Prospective controlled studies are needed to confirm our data.

Bevacizumab (BV), a neutralizing monoclonal antibody against the vascular endothelial growth factor ligand, is recognized as a potent anti-angiogenic agent with antitumor activity. The aim of this single-center, retrospective, longitudinal study was to investigate the possible predictive value of baseline demographic, clinical and laboratory parameters for early 3-month response to BV therapy in patients with recurrent glioma. Forty-nine patients with recurrent glioma received BV at 10 mg/kg intravenously every 3 weeks alone or in association with chemotherapy were included in this study. Blood samples were collected from all patients before the first (baseline), the second and the third administration of BV. After 3 months of BV therapy, patients with partial response were defined as responders whereas patients with stable or progressive disease were defined as non-responders. The median overall follow-up was 8 months (range 1-73), the median overall survival (OS) was 8 months (95% CI 6-10) and the median progression free survival (PFS) was 4 months (95% CI 3-5). Thirty-five % of patients were responders and showed significantly lower von Willebrand factor (VWF) levels than non-responders at all sample times (p

Until now, only one gestational tumefactive demyelinating lesion (TDL) has been described. Here we report two TDL cases occurring during and after the pregnancy. A 26-year-old 6-week pregnant woman developed a 3-cm left frontotemporoparietal subcortical TDL with inhomogeneous partial enhancement. Brain biopsy revealed a subacute demyelinating lesion with abundant macrophages and mild chronic perivascular inflammatory infiltrates. She also had femoralpopliteal deep vein thrombosis. During the 4-year follow-up, magnetic resonance imaging showed only residual biopsied TDL. The second case was a 41-year-woman affected by both multiple sclerosis (MS) and rheumatoid arthritis who developed a 2-cm right anterior corona radiata TDL with sporadic gadolinium-enhancing "annular spots" eight months after delivery. After steroid therapy at the 6-month radiological follow-up, this TDL was half-reduced. Five years earlier, at the beginning of her MS, she already had a 2-cm TDL with incomplete ring enhancement. These two described TDLs formed in prothrombotic conditions and were likely representative of thromboinflammation around and inside the small-medium veins.

Morvan's syndrome (MoS) is a rare, complex neurological disorder characterized by neuromyotonia, neuropsychiatric features, dysautonomia and neuropathic pain. The majority of MoS cases have a paraneoplastic aetiology, usually occurring prior to the diagnosis of the underlying tumour and showing improvement following its treatment. The present study reports the case of a 35-year-old Caucasian male patient who was diagnosed with stage IVA thymoma. Thymectomy, lung resection, diaphragmatic pleurectomy and pericardio-phrenectomy were performed 6 months after neoadjuvant chemotherapy. The pathological evaluation revealed a type B2-B3 thymoma with focal squamous differentiation. Two years later, the patient underwent new surgical treatment for a local recurrence of the same histological type, and 4 weeks later, the patient presented with complex neurological symptoms compatible with MoS, including neuromyotonia, neuropsychiatric features, dysautonomia and neuropathic pain. Electromyography was compatible with a diagnosis of neuromyotonia. Brain magnetic resonance imaging scan and tests for serum anti-acetylcholine receptor, anti-striated muscle antibodies and anti-30-kDa titin fragment antibodies were all negative, whereas tests for anti-voltage-gated potassium channel (VGKC)-complex antibodies (333.3 pmol/l), anti-leucine-rich glioma inactivated protein 1 and anti-contactin-associated protein-like 2 antibodies were positive. The patient underwent 3 cycles of intravenous administration of immunoglobulins (0.4 g/kg/day for 5 days every 4 weeks) with little clinical and electrophysiological improvement. We speculated that the late onset of the symptoms in the present patient may have been triggered by an increase in the serum level of anti-VGKC antibody, which was caused by the surgery performed for the treatment of recurrent thymoma. To the best of our knowledge, the present report is the first case of MoS associated with this histological type of thymoma uncommonly occurring upon surgical treatment of recurrent thymoma.

Background Though the Expanded Disability Status Scale (EDSS) is commonly used to assess disability level in relapsing-remitting multiple sclerosis (RRMS), the criteria defining disability progression are used for patients with a wide range of baseline levels of disability in relatively short-term trials. As a result, not all EDSS changes carry the same weight in terms of future disability, and treatment benefits such as decreased risk of reaching particular disability milestones may not be reliably captured. The objectives of this analysis are to assess the probability of confirmed disability worsening to specific EDSS milestones (i.e., EDSS scores ≥3.0, ≥4.0, or ≥6.0) at 288 weeks in the Tysabri Observational Program (TOP) and to examine the impact of relapses occurring during natalizumab therapy in TOP patients who had received natalizumab for ≥24 months. Methods TOP is an ongoing, open-label, observational, prospective study of patients with RRMS in clinical practice. Enrolled patients were naive to natalizumab at treatment initiation or had received ≤3 doses at the time of enrollment. Intravenous natalizumab (300 mg) infusions were given every 4 weeks, and the EDSS was assessed at baseline and every 24 weeks during treatment. Results Of the 4161 patients enrolled in TOP with follow-up of at least 24 months, 3253 patients with available baseline EDSS scores had continued natalizumab treatment and 908 had discontinued (5.4% due to a reported lack of efficacy and 16.4% for other reasons) at the 24-month time point. Those who discontinued due to lack of efficacy had higher baseline EDSS scores (median 4.5 vs. 3.5), higher on-treatment relapse rates (0.82 vs. 0.23), and higher cumulative probabilities of EDSS worsening (16% vs. 9%) at 24 months than those completing therapy. Among 24-month completers, after approximately 5.5 years of natalizumab treatment, the cumulative probabilities of confirmed EDSS worsening by 1.0 and 2.0 points were 18.5% and 7.9%, respectively (24-week confirmation), and 13.5% and 5.3%, respectively (48-week confirmation). The risks of 24- and 48-week confirmed EDSS worsening were significantly higher in patients with on-treatment relapses than in those without relapses. An analysis of time to specific EDSS milestones showed that the probabilities of 48-week confirmed transition from EDSS scores of 0.0–2.0 to ≥3.0, 2.0–3.0 to ≥4.0, and 4.0–5.0 to ≥6.0 at week 288 in TOP were 11.1%, 11.8%, and 9.5%, respectively, with lower probabilities observed among patients without on-treatment relapses (8.1%, 8.4%, and 5.7%, respectively). Conclusions In TOP patients with a median (range) baseline EDSS score of 3.5 (0.0–9.5) who completed 24 months of natalizumab treatment, the rate of 48-week confirmed disability worsening events was below 15%; after approximately 5.5 years of natalizumab treatment, 86.5% and 94.7% of patients did not have EDSS score increases of ≥1.0 or ≥2.0 points, respectively. The presence of relapses was associated with higher rates of overall disability worsening. These results were confirmed by assessing transition to EDSS milestones. Lower rates of overall 48-week confirmed EDSS worsening and of transitioning from EDSS score 4.0–5.0 to ≥6.0 in the absence of relapses suggest that relapses remain a significant driver of disability worsening and that on-treatment relapses in natalizumab-treated patients are of prognostic importance.

The process of finding new therapeutic indications for currently used drugs, defined as ‘repurposing’, is receiving growing attention. Chloroquine and hydroxychloroquine, with an original indication to prevent or cure malaria, have been successfully used to treat several infectious (HIV, Q fever, Whipple’s disease, fungal infections), rheumatological (systemic lupus erythematosus, antiphospholipid antibody syndrome, rheumatoid arthritis, Sjogren’s syndrome), and other immunological diseases. Indeed, they have anti-inflammatory, immunomodulating, anti-infective, antithrombotic, and metabolic effects. Among the biological effects of chloroquine and hydroxychloroquine, it is important to highlight their antitumoral properties, likely due to their strong antiproliferative, antimutagenic, and inhibiting autophagy capacities. These effects make these drugs a possible option in the treatment of several tumors in association with radiotherapy and chemotherapy. Finally, the repurposing of chloroquine and hydroxychloroquine is currently being examined for neurological diseases such as neurosarcoidosis, chronic lymphocytic inflammation with pontine perivascular enhancement responsive to corticosteroids, and primary progressive multiple sclerosis. Several ongoing clinical trials have been testing these drugs in non-neoplastic and neoplastic diseases. Moreover, the well-demonstrated good tolerability of chloroquine and hydroxychloroquine make them safe even during pregnancy. Gastrointestinal and cutaneous manifestations are considered not to be serious, while retinal, neuromuscular, and cardiac toxicities are classified as serious adverse events.

Background/Aims: The relationship between multiple sclerosis (MS) and anemia has not been clarified sufficiently. In this retrospective, cross-sectional, case-control study we evaluated in MS patients: (1) prevalence of anemia relative to sex- and age-matched controls; (2) relationships between patients' demographic, clinical and drug-related characteristics and anemia; (3) effect of anemia on the risk of developing MS. Methods: 187 consecutive MS patients (51 males, mean age (±SD) 44.5 ± 10.7 years) and 200 controls (56 males, mean age 45.5 ± 12 years) were included in the study. Anemia was defined as hemoglobin Results: There was a significant difference in the prevalence of anemia between MS patients and controls (35 (18.7%) and 19 (9.5%), respectively, p = 0.009). We did not find any association between patients' characteristics and anemia. The occurrence of anemia increased more than twice the risk of developing MS (odds ratio: 2.19, 95% confidence interval 1.19-4.0). Conclusion: Our study showed a consistent association between anemia and MS.

An upstream region from the transcription initiation site to -177 base pairs (bp) of the human alpha-cardiac actin gene directs the transient expression of a bacterial chloramphenicol acetyltransferase (CAT) gene only in muscle cells (A. Minty and L. Kedes, Mol. Cell. Biol. 6:2125-2136, 1986). We modified this promoter region by additional 5' deletions, linker-scanning mutations, and insertion-deletion mutations and demonstrated that the asymmetrical sequences in and adjacent to two CArG [for CC(A + T rich)6GG] motifs, located at -140 and -100 bp, play an important positive role in transcription. The significant impairment of transcriptional activity that accompanies the disruption of one CArG box region can be restored by either. This demonstrated that these two elements interact in a mutually dependent and similar manner. Furthermore, a DNA fragment that includes the CArG boxes had significant competitive activity for transcription directed by the alpha-cardiac actin promoter in an in vivo competition assay. We conclude that the two sequences around each CArG box may interact with the same class of trans-acting positive factor(s) and that these interactions may mediate muscle-specific expression. Each of the two CArG regions appears to be bound independently by such a positive factor(s), and the regions support high-level transcription in a synergistic manner. The transcriptional activity of this regulatory region is proportional to its distance from a TATA box (at -30 bp) and is strictly orientation dependent relative to the direction of transcription. Therefore this upstream region is not an enhancer but is a tissue-specific regulatory upstream element.

In this retrospective case-control study, we compared the number of circulating lymphocyte subsets among 31 healthy controls, 18 naive and 40 antiretroviral-treated HIV patients, 28 untreated and 18 treated relapsing-remitting multiple sclerosis (MS) patients. Lymphocyte subsets were no different between untreated MS patients and controls. Untreated and treated MS had a lower CD8+ count and a higher CD4+ number compared to untreated and treated HIV patients except similar CD4+ number between treated MS and HIV patients. CD4/CD8 ratio was lower in female HIV non-responders and in relapsing MS women compared, respectively, to female HIV responders and remitting MS women, and there were no differences in men.

The exact prevalence and pathogenic role of antiphospholipid antibodies (aPL) in multiple sclerosis (MS) remain unclear. This observational laboratory-blinded study evaluated the rate of aPL positivity in healthy controls and MS patients in different disease phases to recognize their frequency and possible pathogenic meaning. Reactivity for anti-cardiolipin, anti-β2 glycoprotein I, anti-prothrombin, anti-annexin V (IgG and IgM) was studied by enzyme immunoassays in 60 healthy controls and 100 consecutive MS patients [58 relapsing–remitting (RR) patients in remission, 26 RR patients in relapse, and 16 secondary progressive patients]. The overall rate of positivity for at least one aPL was significantly higher in MS patients compared to controls (32 % vs. 7 %, respectively, p

In the original article, the names of authors Mariantonia Carosi and Tatiana Koudriavtseva were incorrectly captured, and author Francesco Cognetti's affiliation was incorrect. The information is correctly shown here.

Several studies have suggested a pathogenetic role of paraproteinaemias in PNS damage. Over the few last years, the presence of symptomatic or subclinical PNS lesions in CNS diseases like multiple sclerosis has been described. On the other hand, CNS demyelinating lesions and cervical atrophy have been re- ported in patients affected by chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Very few cases of MGUS associated with CNS disease alone or with both CNS and PNS disease have been re- ported. Since 1999, we have been studying 16 patients (8 M, 8 F), with a mean age 60.2 ± 13.4, affected by MGUS associated with symptomatic neurological central and/or peripheral diseases. Patients affected with lymphomas, lupus erithematosus and other immunological diseases were excluded. Involvement of both PNS and CNS was not associated to a particular type of paraproteinemia: monoclonal IgM were found in 8 patients; monoclonal IgG in 6 patients and mono- clonal IgA in 1 patient and Igl in 1 patient. High anti- nervous system autoantibodies were found in 10/16 patients and antiMAG antibodies were detected in patients with paraproteinemic demyelinating neuropathy (PDN). High reactivity anti-nervous system might support the hypothesis of a pathogenetic role of MGUS in these neurological diseases. Nevertheless, at present, we cannot exclude that there is only a circumstantial association between MGUS and neurological damages, particularly concerning CNS.

Recently, Yildiz et al. reported the occurrence of acute hemorrhagic leukoencephalitis (AHLE) in a patient with pluriannual relapse-remitting multiple sclerosis (MS) after 1 month of high-dose interferon-β-1a treatment. The authors raised the question whether this case may be a hyperacute form of acute disseminated encephalomyelitis (ADEM) or a rare hemorrhagic evolution of tumefactive demyelination (TD), both unusual in the course of MS (1). They concluded that AHLE occurrence was unrelated to the underlying MS since hemorrhage has not been found in neuropathological patterns of both MS and TD. Although two published case reports of TD with hemorrhage in the course of fingolimod and natalizumab therapies (brain biopsy was not performed) have been mentioned in the paper, the potential predisposing effect of interferon-β therapy on the AHLE development has not been hypothesized.

Testicular cancer (TC) is the most common tumor of young ales and its incidence has approximately doubled worldwide ver the past 40 years, without a comprehensible etiology for the bserved increase [1,2]. Both environmental and genetic factors are ikely to be involved [2]. Germ cell tumors (GCTs) are malignancies erived from primitive stem-cells and are divided into two cateories based on histology: tumors included pure seminoma and umors with some component of non-seminoma (NS), such as tertoma, embryonal carcinoma, choriocarcinoma and yolk sac tumor. CTs are curative diseases, with cure rates of over 80% [3]. However, 8% of patients with metastatic NSGCTs have poor-risk features hat result in cure rates of only about 50% at 5 years [3]. Negaive prognostic features are the non-seminoma histology together ith mediastinal primary site, the presence of non-pulmonary isceral metastases, or severe increase of serum tumor markers lphafetoprotein (AFP), human chorionic gonadotropin (HCG), and actate dehydrogenase (LDH). However the presence of a medistinal primary site and the presence of central nervous system CNS) metastases appear to confer the greatest risk of mortality. etastatic GCTs can be classified into good-, intermediate-, and

So far, no studies have been conducted to evaluate possible correlations between lipid/lipoprotein levels and the anti-phospholipid antibody (aPL) positivity in multiple sclerosis (MS). In this cross-sectional study, we aimed to investigate the relationships between serum lipid profile and aPL positivity rates in MS patients, and their possible differences among secondary-progressive MS (SPMS) patients, relapsing-remitting MS patients in remission (REM) and in relapse (REL). We included 16 SPMS, 58 REM and 26 REL. Their sera were tested for aPL (anti-cardiolipin, anti-β2glycoproteinI, anti-prothrombin, anti-annexinV), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) and lipoprotein(a) levels. High TC levels were more frequent in SPMS patients than other groups (p=0.05). The REL had significantly higher rates of positivity for anti-β2glycoproteinI IgM (p

Multiple sclerosis (MS) is a chronic demyelinating inflammatory disease of the central nervous system (CNS) with multi-factorial pathogenesis that includes genetic and environmental factors. A primary brain tumor is a neoplasm developing from the cells of the brain. There is high heterogeneity of primary brain tumors (about 100 different types); however, most of them develop from the glial cells. Although several types of brain tumors have been widely described in association with MS (1–20), including astrocytoma (5, 9), oligodendroglioma (12, 17), and glioblastoma (3, 11, 14, 18), it is not clear whether their occurrence is accidental or consequent to causal events. Moreover, it is not completely defined if MS and brain tumors, when associated, have a different course. The true incidence of brain tumors in MS patients is difficult to define because the diagnosis of a brain tumor in MS patients may seem more frequent than in the general population due to frequent neuroimaging scans performed in these patients (21). At the same time, pseudo-tumoral MS lesions may resemble gliomas, and conversely, early stage gliomas may resemble MS. Brain tumors in MS patients may be diagnosed later or even post-mortem (22), especially in patients with progressive MS, since the new symptoms may be attributed to the gradual clinical progression of MS rather than to the slow growing of tumor itself (23). A recent study reported that MS patients have a decreased overall cancer risk, but an increased risk for brain tumor (24). If immunosuppressive treatment for MS might promote cancerogenesis is still matter of debate, it is difficult to explain on this basis why MS patients have a decreased overall cancer risk and an increased risk only for brain and genitourinary tract tumors (24). A successive systematic analysis showed no increased or decreased risks for glioma in MS patients, while an increased risk was found for meningioma, as a result of incidental findings (25). Moreover, several autoimmune diseases influence negatively the survival in glioma and meningioma, likely due to pre-existent disability or treatment limitations (25).