Multiple sclerosis (MS) commonly causes eye movement abnormalities that may have a significant impact on patients' disability. Inflammatory demyelinating lesions, especially occurring in the ...posterior fossa, result in a wide range of disorders, spanning from acquired pendular nystagmus (APN) to internuclear ophthalmoplegia (INO), among the most common. As the control of eye movements is well understood in terms of anatomical substrate and underlying physiological network, studying ocular motor abnormalities in MS provides a unique opportunity to gain insights into mechanisms of disease. Quantitative measurement and modeling of eye movement disorders, such as INO, may lead to a better understanding of common symptoms encountered in MS, such as Uhthoff's phenomenon and fatigue. In turn, the pathophysiology of a range of eye movement abnormalities, such as APN, has been clarified based on correlation of experimental model with lesion localization by neuroimaging in MS. Eye movement disorders have the potential of being utilized as structural and functional biomarkers of early cognitive deficit, and possibly help in assessing disease status and progression, and to serve as platform and functional outcome to test novel therapeutic agents for MS. Knowledge of neuropharmacology applied to eye movement dysfunction has guided testing and use of a number of pharmacological agents to treat some eye movement disorders found in MS, such as APN and other forms of central nystagmus.
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.
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.
Few studies have evaluated whether the retina is involved in migraine through the evaluation of retinal nerve fiber layer (RNFL) examined with ocular coherence tomography (OCT) with conflicting ...results. Aim of this case–control study is to evaluate the retina and the choroid in migraine. Patients having migraine with aura (MwA) or without aura (MoA) and chronic migraine (CM) were evaluated. Age- and sex-matched normal subjects were selected as healthy controls (HC). Patients and HC were examined with OCT. RNFL, ganglion cell layer (GCL), foveal thickness (FT), choroidal thickness (CT) and total macular volume (TMV) were calculated for right eyes (RE) and left eyes (LE). Seventy-seven patients (62 women; 80.5%), 21 MoA, 12 MwA, 44 CM and 42 HC were enrolled in the study. Patients compared to HC had a significant reduction of RNFL (RE: 91.2 ± 9.2 vs 99.3 ± 7.5 μm;
p
< 0.001. LE: 93.3 ± 8.7 vs 100.2 ± 6.5 μm;
p
< 0.001). GCL (RE: 80.6 ± 6.4 vs 86.9 ± 2.1 μm;
p
< 0.0001. LE: 81.5 ± 5.7 vs 87.1 ± 2.6 μm;
p
< 0.0001) and CT (RE: 286.4 ± 31.4 vs 333.2 ± 3.1 μm;
p
< 0.0001. LE: 287.2 ± 31.6 vs 334.5 ± 4.1 μm;
p
< 0.0001) were thinner in patients compared to HC. Moreover, CM showed reduction of RNFL and of GCL compared to the other migraineurs. Finally, we found a significant inverse correlation between RNFL thickness and total number of headache attacks per months. Our data suggest the involvement of retina and choroid in migraineurs, especially in the CM group. Although migraine is an episodic and recurrent disease, its chronic nature might cause permanent structural abnormalities involving not only the brain, but also the retina.
The prevalence of pain in Multiple Sclerosis (MS) is estimated to be between 29-86% depending on various stages of the disease. According to a recent mechanism-based classification, MS pain syndromes ...include ongoing extremity pain, trigeminal neuralgia, and Lhermitte's phenomenon, painful tonic spasms and spasticity pain, pain associated with optic neuritis, musculoskeletal pain, migraine, and treatment-induced pain.
Pharmacological approaches for MS pain include anticonvulsants, antidepressants, botulinum toxin, cannabinoids, muscle relaxants, opioid analgesics, and intrathecally administered baclofen. It has been reported that pharmacological treatments have poor efficacy and alarming side effects. For these reasons, non-pharmacological interventions, either alone or in combination with pharmacological treatments are commonly used in clinical practice. Examples of these interventions include electrical or chemical neurostimulation therapy, exercise, and psychological approaches. This is discussed in more detail herein.
The management of MS pain can be challenging due to the natural course of the disease and the lack of a definite cure. Recommendations based on rigorous scientific methods for MS pain treatment are unavailable. Thus, clinicians should consider available treatment regimens based on efficacy, safety, cost, and the clinical complexity of the patient. The use of therapeutic approaches combining pharmacological and non-pharmacological treatments may help to reduce the risk of overuse and mitigate the complaint of simultaneous and multiple therapies.
Abstract
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.
The complexity of understanding cancer risk in MS is increased by inconsistencies in study design, and the lack of age-, sex-, and ethnicity-specific risk estimates. Aims of our study were to ...estimate the incidence of cancers in the MS population of Catania (Italy) and to evaluate the impact of disease-modifying treatments (DMTs) in cancer risk.
We screened 2,730 PwMS according to the MS criteria of Mc Donald 2010 referring to MS center of Catania in the period between 2003 and 2013. We matched database of MS patients with the Integrated Cancer of Catania-Messina-Siracusae-Enna. We calculated age and sex specific standardized incidence ratios (SIR) and the relative risk (RR) of developing cancer in MS patients treated with at least two different DMTs compared to who received one or no treatment.
Out of 2,730, 1,180 MS patients (67.1% females; mean age 41.2 ± 12.9) were enrolled. We found 36 cancers. Global SIR was 1.18 (CI95% 0.78-1.58), with a significantly higher risk in men with a range age of 20 to 50 years 2.84; (CI95% 1.59-4.09) and in women over 50 years 1.82 (CI95% 1.08-2.55). RR of developing cancer was 1.99 (CI95% 1.14-3.45) in MS patients switching one DMT and 3.38 (CI95% 1.83-6.22) in who switched at least twice.
Our results demonstrated that cancer risk was not increased in our MS population; but age and sex different distribution may partly drive cancer risk. Higher cancer risk in MS patients switching more than two DMTs should take into account in treatment decision making.
Skin lesions represent lesions that result in loss of tissues and their joints and often this cutaneous process is a primary or secondary consequence of structural changes in the same skin surface. ...Type 2 diabetic subjects developing chronic skin lesions in the lower limbs in the western world are steadily increasing. We conducted a study on the etiologic incidence of chronic skin lesions in type II diabetic subjects in the lower limbs compared to subjects with chronic skin lesions (controls).
Thirty subjects (group "A") with Chronic Skin Lesions (CSL controls) (19 F-11M, mean age 67.5±7.2) in the lower limbs were admitted to our study according to a randomization scheme and compared a thirty (group "B") type II diabetic patients (18F-12M, mean age 73.5±4.9) with chronic skin lesions (CSL). These two groups "A" and "B" have been studied and compared on the basis of infectious etiology responsible for the infectious skin process.
In the subjects of the "A" group we found a positive bacteriological colony test of 9 examinations corresponding to the total 30.0%. In the group called "B" we obtained a colony test positive of 12 subjects over 30 corresponding to 40.0% of the examinations. For the number of bacterial species identified in the "A" group we obtained 7 monomicrobial and 2 poly microbial bacteriological tests, while in the "B" group we observed 3 mono microbial and 9 poly microbial tests. All bacteriological isolates showed "in vitro" sensitivity to satisfactory aminoglycosides with MICs range of 0.78- 1.56mg/L.
Data from this study show a different etiology among diabetic subjects than nondiabetic subjects. In fact, in the "B" group, more poly microbial bacteriological findings are found in positive culture studies with subjects in group "A". This phenomenon confirms an alteration of the skin microbiome of diabetic subjects with modification of the "opportunistic role" of some species of the skin bacterial flora.
Essential tremor (ET) represents a heterogeneous condition which may overlap with Parkinson disease (PD) even at early stages, by sharing some subtle clinical aspects. Longstanding ET demonstrated ...also higher risk of developing PD, especially with a Tremor-dominant (TD-PD) phenotype. Therefore, differential diagnosis between ET and early PD could be quite challenging. Optical coherence tomography (OCT) has been recognized as a reliable tool to assess the retina as a proxy of neurodegeneration. We aimed to explore the possible role of retinal assessment in differential diagnosis between ET and early PD.
Macular layers and peripapillary retinal nerve fiber layer (RNFL) thickness among ET, early PD, and healthy controls (HCs) were assessed using OCT.
Forty-two eyes from 23 ET, 41 eyes from 21 early PD, and 33 eyes from 17 HCs were analyzed. Macular RNFL, ganglion cell layer, inner plexiform layer, and inner nuclear layer were thinner in PD as compared with ET and even more in HCs. Differences between ET and PD were more evident when considering the TD-PD subgroup, especially for RNFL. Among ET patients, thickness of the inner macular layers showed negative linear relationship with both age at onset and disease duration. Peripapillary temporal quadrant thinning was found in ET compared with HCs.
Macular inner retina was thinner in patients with ET and early PD compared with HCs. These findings suggest that the retinal assessment may have a utility in the differential diagnosis between ET and PD.
Ocrelizumab is a recombinant humanized monoclonal antibody selectively targeting CD20-expressing B cells. The effect of ocrelizumab on primary progressive multiple sclerosis (PPMS) has been evaluated ...during phase 3 trials that enrolled patients under 55 years with a maximum Expanded Disability Status Scale (EDSS) of 6.5. However, little is known on older disabled patients with longer disease duration. We aimed to assess the clinical effectiveness of ocrelizumab in PPMS patients out of the ORATORIO eligibility criteria. This multicenter retrospective study collected data about the effectiveness of ocrelizumab in PPMS patients who received treatment between May 2017 and June 2022 in the Italian MS centers contributing to the Italian MS Registry who adhered to the Compassionate Use Program. The confirmed EDSS worsening (CEW) (defined as either a ≥ 1-point or ≥ 2-point increase in EDSS score from baseline that was confirmed at T12 and T24) was calculated. At the date of data extraction, out of 887 PPMS patients who had received ocrelizumab, 589 (mean age 49.7 ± 10.7 years, 242 (41.1%) females) were enrolled. The mean follow-up period was 41.3 ± 12.3 months. A total of 149 (25.3%) received ocrelizumab according to the ORATORIO criteria (ORATORIO group) and 440 (74.7%) outside the ORATORIO criteria (non-ORATORIO group). No differences in terms of cumulative probabilities of 12 and 24 months of CEW of ≤ 1 point were found between ORATORIO and non-ORATORIO groups. Cox regression analyses showed that age older than 65 years (HR 2.51, 25% CI 1.07–3.65;
p
= 0.01) was associated with higher risk of CEW at 24 months. Patients not responding to ORATORIO criteria for reimbursability may benefit from ocrelizumab treatment, as disease activity, disease duration, and EDSS seem to not impact the disability outcome. Our results may suggest to extend the possible use of this powerful agent in selected patients under the age of 65 years.
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