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Introduction: Retinal nerve fiber layer (RNFL) thickness is a promising biomarker of axonal loss and a potential outcome predictor in Multiple Sclerosis (MS). Cognitive impairment (CoI) exhibits a high prevalence in patients with MS (pwMS), even in the early phases of the disease. Our aim was to explore the role of RNFL thickness as a predictor of physical and cognitive disability in pwMS. Methods: All newly diagnosed pwMS referred to the MS centre of the University-Hospital "Policlinico-San Marco" between 2015–2019 were evaluated at baseline and at 3 years. RNFL and ganglion cell layer (GCL) thickness for right (r.e.) and left eyes (l.e.) were measured with Optical Coherence Tomography (OCT). Disability level and cognitive profile were assessed, using the Expanded Disability Status Scale (EDSS) and the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) battery, respectively. Results: We consecutively enrolled 487 pwMS, including 68 (14.0%) with primary progressive MS (PPMS). At baseline, RNFL and GCL were bilaterally thinner in PPMS (r.e. 90.4 ± 12.7; l.e. 90.2 ± 13.5, and r.e. 80.1 ± 11.2; l.e. 80.3 ± 12.6, respectively) compared to relapsing–remitting MS (RRMS) (r.e. 94.6 ± 13.1; l.e. 94.3 ± 14.8, and r.e. 85.1 ± 9.5; l.e. 84.9 ± 9.3, respectively) (p < 0.01). Both groups exhibited reduced RNFL and GCL thickness, worse cognitive performance and higher EDSS scores at 3-years follow-up compared with baseline. RNFL thickness ≤ 88.0 μm was an independent predictor of CoI (OR = 5.32; 95% CI = 1.84–9.12; p = 0.02) and disability worsening (OR = 3.18; 95% CI = 1.21–10.33; p = 0.05). Discussion: RNFL thickness, as a biomarker of neurodegeneration, could be considered a predictive biomarker of cognitive degeneration and physical disability in MS. [ABSTRACT FROM AUTHOR]

Background: Previous studies attempted to define the best threshold for κ free light chains (κFLC) index, confirming higher sensitivity (Se) but less specificity (Sp) compared with IgG oligoclonal bands (OCB) for the diagnosis of MS. Objective: To evaluate the diagnostic accuracy of different κFLC index intervals in a miscellaneous cohort of neurological patients, proposing a procedural flowchart for MS diagnosis. Methods: We analyzed data from 607 patients diagnosed with MS (179), CIS (116), other inflammatory (94) or non-inflammatory neurological diseases (218). Measures of diagnostic accuracy were reported for different potential thresholds of κFLC index, and for IgG OCB and IgG index. Binary logistic regression was to used to calculate the odds of being diagnosed with MS based on each increase of κFLC index. Results: CSF IgG OCB showed 72.2% Se (CI 95% 68.4–75.7) and 95.2% Sp (CI 95% 93.1–96.7) in discriminating between MS/CIS and controls, with an AUC of 0.84 (CI 95% 0.80–0.87). The highest diagnostic accuracy was reported for κFLC index cut-off of 5.0 (Se = 85.4%, Sp = 90.4%, AUC = 0.88), while a threshold of 11.0 exhibited higher Sp (95.5%, 95% CI 93.1–97.1) than IgG OCB. AUCs for all thresholds between 4.25 and 6.6 were not significantly different from each other, but were significantly higher than the AUC of IgG OCB (p < 0.05). The odds of being diagnosed with MS/CIS increased by 17.1% for each unit increase of κFLC index (OR = 1.17; 95% CI 1.12–1.23; p < 0.001). Conclusion: κFLC index performed better than CSF IgG OCB in supporting the diagnosis of MS/CIS, with the advantage of being a cost-effective and quantitative analysis. [ABSTRACT FROM AUTHOR]

Background: Evidence of the cost-effectiveness of telemedicine (TM) for the management of Multiple Sclerosis (MS) has been provided recently. However, some doubts persist about the accuracy of neurological examinations performed remotely. Objectives: This study investigated the reliability of neurological evaluations performed through TM in mild MS patients as compared with standard in-person visits. Methods: In total, 76 patients with relapsing–remitting MS and Expanded Disability Status Scale (EDSS) ≤ 3.5 were consecutively recruited. Of them, 40 patients (52.6%) accepted to undergo both in-person and TM evaluations with independent examiners within 48 h. We alternatively asked patients to assure or not the presence of a caregiver during TM visits. A satisfaction questionnaire was administered to all participants. Results: The inter-rater agreement attributed by two independent neurologists during TM visit was high (κ > 0.80) for EDSS and Functional Systems (FS) scores. Moderate agreement between TM and in-person evaluations emerged for pyramidal (κ = 0.57; p < 0.001), brainstem (κ = 0.57; p < 0.001), bowel and bladder (κ = 0.54; p < 0.001) and sensory (κ = 0.51; p < 0.001) FS scores, higher in patients providing the support of a caregiver. A good reliability was reported for EDSS scores computed during remote and in-person visits (ICC = 0.83; 95% CI 0.70–0.91; p < 0.001). Conclusions: Despite the complexity of neurological examination, TM could be useful in monitoring MS patients with low disability. [ABSTRACT FROM AUTHOR]

On 11 March 2020, the World Health Organization declared the coronavirus disease 19 (COVID-19) outbreak a pandemic. In this context, several studies and clinical trials have been conducted since then, and many are currently ongoing, leading to the development of several COVID-19 vaccines with different mechanisms of action. People affected by multiple sclerosis (MS) have been considered high-risk subjects in most countries and prioritized for COVID-19 vaccination. However, the management of MS during the COVID-19 pandemic has represented a new challenge for MS specialists, particularly because of the initial lack of guidelines and differing recommendations. Despite an initial hesitation in prescribing disease-modifying drugs (DMDs) in naïve and already treated patients with MS, most national neurology associations and organizations agree on not stopping treatment. However, care is needed especially for patients treated with immune-depleting drugs, which also require some attentions in programming vaccine administration. Many discoveries and new research results have accumulated in a short time on COVID-19, resulting in a need for summarizing the existing evidence on this topic. In this review, we describe the latest research results on the immunological aspects of SARS-CoV-2 infection speculating about their impact on COVID-19 vaccines' mechanisms of action and focused on the management of MS during the COVID pandemic according to the most recent guidelines and recommendations. Finally, the efficacy of COVID-19 and other well-known vaccines against infectious disease in patients with MS on DMDs is discussed. [ABSTRACT FROM AUTHOR]

Background: The Coronavirus disease 2019 (COVID-19) caused by the new Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has become a pandemic, affecting the therapeutic management for Multiple Sclerosis (MS). Any decision regarding the discontinuation of high-potency agents for moderate and highly active MS should be carefully evaluated, taking into account the potential risk of rebound of the disease. In particular, no data about clinical outcome of patients with MS receiving Natalizumab (NTZ) during active COVID-19 infection have been reported yet. Cases presentation: We reported on 6 patients treated with NTZ for relapsing MS during active COVID-19 infection, who recovered without reporting any worsening or new symptoms. Most of the patients were asymptomatic, with the exception of one patient who had a slight worst COVID-19 clinical course. No patients received O2-therapy or required intensive care. No neurological complications were observed. Conclusions: This paper reported the clinical outcome of patients with MS receiving NTZ during active COVID-19 infection. This case series suggests that treatment with NTZ during pandemic is relatively safe and might be continued in selected patients who are infected by COVID-19, thereby reducing the risk of MS disease rebound. [ABSTRACT FROM AUTHOR]

Background: The Coronavirus disease 2019 (COVID-19) caused by the new Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has become a pandemic, affecting the therapeutic management for Multiple Sclerosis (MS). Any decision regarding the discontinuation of high-potency agents for moderate and highly active MS should be carefully evaluated, taking into account the potential risk of rebound of the disease. In particular, no data about clinical outcome of patients with MS receiving Natalizumab (NTZ) during active COVID-19 infection have been reported yet.Cases Presentation: We reported on 6 patients treated with NTZ for relapsing MS during active COVID-19 infection, who recovered without reporting any worsening or new symptoms. Most of the patients were asymptomatic, with the exception of one patient who had a slight worst COVID-19 clinical course. No patients received O2-therapy or required intensive care. No neurological complications were observed.Conclusions: This paper reported the clinical outcome of patients with MS receiving NTZ during active COVID-19 infection. This case series suggests that treatment with NTZ during pandemic is relatively safe and might be continued in selected patients who are infected by COVID-19, thereby reducing the risk of MS disease rebound. [ABSTRACT FROM AUTHOR]

Idiopathic intracranial hypertension is a neurological syndrome determined by a rise in intracranial pressure without a detectable cause. Course and prognosis may be changeable, requiring a multidisciplinary approach for its diagnosis and management. Although its precise pathogenesis is still unknown, many studies have been carried out to define the possible causal and associated factors, such as retinoids, steroid hormones, body mass index and recent weight gains, cytokines and adipokines levels. The clinical presentation can be variable including chronic headache, disturbance of vision, diplopia and tinnitus. Even if papilloedema is considered the most specific sign, it could not be observed in more than 5% of patients during the evaluation of the fundus oculi. Neuroradiological signs acquire greater importance in patients who do not present papilloedema and may suggest the diagnosis of idiopathic intracranial hypertension. Other assessments can be useful in the diagnostic process, such as optical coherence tomography, visual evoked potentials, ocular ultrasonography and fundus fluorescein angiography and autofluorescence. Nonetheless, cerebrospinal fluid pressure measurement is required to establish a definite diagnosis. Management may be different, since surgical procedures or lumbar punctures are often required when symptoms develop rapidly leading to a loss of visual function. Apart from these cases, patients can be treated with a pharmacological approach and low-calorie diet, but they also need to be monitored over time since relapses years later are not uncommon. [ABSTRACT FROM AUTHOR]

Indeed, a prevalence by 10-14% of IIHWOP among chronic migraine sufferers has been reported, together with some evidence of a different clinical profile exhibited by IIHWOP compared with IIH with papilloedema (IIHWP) [[3]]. In this perspective, it would be very interesting to know the role of the abovementioned molecules discussed by Grech and coworkers in IIHWOP and to understand whether IIHWOP and IIHWP share the same physiopathological processes. This is of interest, since patients with IIHWOP are often chronic headache sufferers and could be more easily underdiagnosed and, consequently, undertreated and not adequately monitored. [Extracted from the article]

Abstract: The IceCube neutrino telescope, completed in December 2010, is a cubic-kilometer scale detector buried under the South Pole ice. Between May 2009 and May 2010, IceCube recorded 32 billion of atmospheric muons generated in air showers produced by cosmic rays in the TeV energy range. This high statistics data sample can be used to look for anisotropy in the arrival directions of the cosmic ray particles at the per-mille level. IceCube observes, for the first time in the southern hemisphere, an energy dependence in the Galactic cosmic ray anisotropy up to a few hundred TeV. This study shows that the same large-scale anisotropy observed at median energies around 20TeV is not present at 400TeV; the anisotropy observed at 400TeV shows substantial differences with respect to that at lower energy. In addition to the large-scale features observed at 20TeV in the form of strong dipole and quadrupole moments, the data include several localized regions of excess and deficit on scales between 10° and 30°. The features observed at both large and small scales are statistically significant, but their origin is currently unknown. [Copyright &y& Elsevier]

Cladosporium infections have a poor prognosis in animals, most likely due to a lack of knowledge about diagnosis and treatment. In this study, we described a case of a lethal Cladosporium allicinum infection in a captive bullfrog (Pyxicephalus adspersus) in Europe. One adult male bullfrog was referred with clinical signs of lethargy and a cutaneous nodule. Fungal infection was suspected on cytology and confirmed by histology and cultural isolation. The mold was identified by molecular methods using partial sequencing of the TEF1α gene and the ITS region of rDNA. Climbazole antifungal treatment was started but the frog died after 30 days, and necropsy was done. Pigmented hyphae and structures consistent with muriform bodies were found on a background of diffuse granulomatous inflammation at cytological and histopathological examinations. Fungal culture revealed the presence of pigmented fungi identified as Cladosporium allicinum only by partial sequencing of the TEF1α gene. A focally extensive granuloma with intralesional hyphae and muriform bodies effacing the architecture of head, liver, kidneys, lungs, and large intestine were retrieved after necropsy. This study is the first Italian report of the occurrence of lethal C. allicinum infection in a frog and highlights the role of this Cladosporium sp. in chromoblastomycosis. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a chronic, inflammatory and immune-mediated disease of the central nervous system (CNS), commonly affecting young adults and potentially associated with life-long disability. About 14 disease-modifying treatments (DMTs) are currently approved for the treatment of MS. However, despite the use of highly effective therapies, some patients exhibit a highly active disease with an aggressive course from onset and a higher risk of long-term disability accrual. In the last few years, several retrospective studies, clinical trials, meta-analyses and systematic reviews have investigated autologous hematopoietic stem cell transplantation (AHSCT) as a possible therapeutic option in order to address this unmet clinical need. These studies demonstrated that AHSCT is a highly efficacious and relatively safe therapeutic option for the treatment of highly active MS. Particularly, over recent years, the amount of evidence has grown, with significant improvements in the development of patient selection criteria, choice of the most suitable transplant technique and clinical experience. In this paper, we present six patients who received AHSCT in our MS center and we systematically reviewed recent evidence about the long-term efficacy and safety of AHSCT and the placement of AHSCT in the rapidly evolving therapeutic armamentarium for MS. [ABSTRACT FROM AUTHOR]

In the last decades, evidence suggesting the direct or indirect involvement of B cells on multiple sclerosis (MS) pathogenesis has accumulated. The increased amount of data on the efficacy and safety of B-cell-depleting therapies from several studies has suggested the addition of these drugs as treatment options to the current armamentarium of disease modifying therapies (DMTs) for MS. Particularly, rituximab (RTX), a chimeric monoclonal antibody directed at CD20 positive B lymphocytes resulting in cell-mediated apoptosis, has been demonstrated to reduce inflammatory activity, incidence of relapses and new brain lesions on magnetic resonance imaging (MRI) in patients with relapsing–remitting MS (RRMS). Additional evidence also demonstrated that patients with progressive MS (PMS) may benefit from RTX, which also showed to be well tolerated, with acceptable safety risks and favorable cost-effectiveness profile. Despite these encouraging results, RTX is currently approved for non-Hodgkin's lymphoma, chronic lymphocytic leukemia, several forms of vasculitis and rheumatoid arthritis, while it can only be administered off-label for MS treatment. Between Northern European countries exist different rules for using not licensed drug for treating MS. The Sweden MS register reports a high rate (53.5%) of off-label RTX prescriptions in relation to other annually started DMTs to treat MS patients, while Danish and Norwegian neurologists have to use other anti-CD20 drugs, as ocrelizumab, in most of the cases. In this paper, we review the pharmacokinetics, pharmacodynamics, clinical efficacy, safety profile and cost effectiveness aspects of RTX for the treatment of MS. Particularly, with the approval of new anti-CD20 DMTs, the recent worldwide COVID-19 emergency and the possible increased risk of infection with this class of drugs, this review sheds light on the use of RTX as an alternative treatment option for MS management, while commenting the gaps of knowledge regarding this drug. [ABSTRACT FROM AUTHOR]

The timed up and go test (TUG) is a widely used clinical test for the evaluation of balance and mobility. An instrumented version of TUG (iTUG) has been proposed to provide quantitative information on TUG performances. Here, we hypothesized that l-dopa may differently influence gait parameters recorded by a portable inertial sensor. To test this idea, we evaluated iTUG test in patients with Parkinson's disease (PD), both in l-dopa OFF and ON state. Twenty-eight PD patients performed the iTUG. Subjects were instructed to perform the task both in practical 'OFF' and 'ON' state. The system differentiated the test in six phases, recording phase durations, three-axial accelerations, average and peak angular speeds during turning. In all patients, sit-to-stand vertical and medio-lateral accelerations together with turning phase duration and angular speeds improved after l-dopa administration, while sit-to-stand and stand-to-sit phases antero-posterior accelerations were less responsive. In PD, l-dopa modulates iTUG in different ways, mostly improving the turning phases and less acting on postural controls during the sit-to-stand and stand-to-sit phases. Our results suggest different involvement of dopaminergic mechanisms on gait as assessed by iTUG. This is important for those aspects which are not improved by pharmacological therapy. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder of the central nervous system (CNS) that causes progressive and irreversible damage in motor neurons. Different causal hypotheses include genetic, viral, traumatic and environmental mechanisms, such as exposure to heavy metals. The aim of this study was to compare metal/metalloid levels in cerebro-spinal fluid of ALS subtypes (spinal vs bulbar clinical onset). This observational study consecutively screened all ALS patients referring to the Neurology Clinic of the University of Catania (Italy). Inductively coupled plasma mass spectrometry (ICP-MS) was used to quantify magnesium (Mg), cuprum (Cu), selenium (Se), iron (Fe), manganese (Mn), vanadium (V), zinc (Zn), alluminium (Al), arsenic (As), cobalt (Co), nickel (Ni), mercury (Hg), lead (Pb), cadmium (Cd) and palladium (Pd) levels. Thirty-seven patients were enrolled (62.2% females), median age of 65 years (IQR: 59–71 years). Thirty-one (83.8%) patients had a spinal onset and 6 (16.2%) a bulbar onset. Se and As levels were higher compared to the reference values (RV) both in spinal and bulbar onset, while Cu was higher than RV only in bulbar onset. Moreover, Cu (129.8 μg/L vs 29.8 μg/L), Fe (54.5 μg/L vs 33.3 μg/L), Mn (3.4 μg/L vs 1.8 μg/L), Zn (46.1 μg/L vs 35.7 μg/L), Al (12.2 μg/L vs 6.7 μg/L), Ni (2.80 μg/L vs 1.40 μg/L), and Pb (0.60 μg/L vs 0.30 μg/L) levels were higher in bulbar than in spinal onset, conversely As was slightly higher in spinal than in bulbar onset (1.40 μg/L vs 1.10 μg/L). Overall, Cu (129 μg/L vs 31 μg/L), Fe (92.2 μg/L vs 32.9 μg/L), Mn (3.35 μg/L vs 1.80 μg/L), Zn (56.5 μg/L vs 35.2 μg/L), Al (14.45 μg/L vs 6.70 μg/L), and Cd (0.40 μg/L vs 0.08 μg/L) levels were higher in patients with disease duration less than 19 months. Our results supported the hypothesis that metals/metalloids with neurotoxic effects could be involved in the etiology of ALS, showing higher levels of Cu, Se and As. Relevant differences in Cu and Mn levels were found between bulbar and spinal onset patients. • The etiology of the amyotrophic lateral sclerosis (ALS) is still unknown. • Metalloids and several heavy metals seem to play a role on ALS pathogenesis. • Our study showed higher levels of Cu, Se and Zn in ALS compared to reference values. • Higher levels of Cu and Mn were found in bulbar onset patients than in spinal onset. [ABSTRACT FROM AUTHOR]