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.
Cognitive impairment is a common and disabling feature of multiple sclerosis (MS), but a precise characterization of cognitive phenotypes in patients with MS is lacking.
To identify cognitive ...phenotypes in a clinical cohort of patients with MS and to characterize their clinical and magnetic resonance imaging (MRI) features.
This multicenter cross-sectional study consecutively screened clinically stable patients with MS and healthy control individuals at 8 MS centers in Italy from January 1, 2010, to October 31, 2019. Patients with MS and healthy control individuals who were not using psychoactive drugs and had no history of other neurological or medical disorders, learning disability, severe head trauma, and alcohol or drug abuse were enrolled.
Participants underwent a neurological examination and a cognitive evaluation with the Rao Brief Repeatable Battery and Stroop Color and Word Test. A subgroup of participants also underwent a brain MRI examination. Latent profile analysis was used on cognitive test z scores to identify cognitive phenotypes. Linear regression and mixed-effects models were used to define clinical and MRI features of each phenotype.
A total of 1212 patients with MS (mean SD age, 41.1 11.1 years; 784 women 64.7%) and 196 healthy control individuals (mean SD age, 40.4 8.6 years; 130 women 66.3%) were analyzed in this study. Five cognitive phenotypes were identified: preserved cognition (n = 235 patients 19.4%), mild-verbal memory/semantic fluency (n = 362 patients 29.9%), mild-multidomain (n = 236 patients 19.5%), severe-executive/attention (n = 167 patients 13.8%), and severe-multidomain (n = 212 patients 17.5%) involvement. Patients with preserved cognition and mild-verbal memory/semantic fluency were younger (mean SD age, 36.5 9.8 years and 38.2 11.1 years) and had shorter disease duration (mean SD 8.0 7.3 years and 8.3 7.6 years) compared with patients with mild-multidomain (mean SD age, 42.6 11.2 years; mean SD disease duration, 12.8 9.6 years; P < .001), severe-executive/attention (mean SD age, 42.9 11.7 years; mean SD disease duration, 12.2 9.5 years; P < .001), and severe-multidomain (mean SD age, 44.0 11.0 years; mean SD disease duration, 13.3 10.2 years; P < .001) phenotypes. Severe cognitive phenotypes prevailed in patients with progressive MS. At MRI evaluation, compared with those with preserved cognition, patients with mild-verbal memory/semantic fluency exhibited decreased mean (SE) hippocampal volume (5.42 0.68 mL vs 5.13 0.68 mL; P = .04), patients with the mild-multidomain phenotype had decreased mean (SE) cortical gray matter volume (687.69 35.40 mL vs 662.59 35.48 mL; P = .02), patients with severe-executive/attention had higher mean (SE) T2-hyperintense lesion volume (51.33 31.15 mL vs 99.69 34.07 mL; P = .04), and patients with the severe-multidomain phenotype had extensive brain damage, with decreased volume in all the brain structures explored, except for nucleus pallidus, amygdala and caudate nucleus.
This study found that by defining homogeneous and clinically meaningful phenotypes, the limitations of the traditional dichotomous classification in MS can be overcome. These phenotypes can represent a more meaningful measure of the cognitive status of patients with MS and can help define clinical disability, support clinicians in treatment choices, and tailor cognitive rehabilitation strategies.
Patient-reported outcomes (PROs) are essential for understanding the effects of MS and its treatments on patients’ lives; they play an important role in multiple sclerosis (MS) research and practice. ...We present the protocol for an observational study to prospectively assess the effect of cladribine tablets on PROs and their correlation to disability and physical activity in adults with highly active relapsing MS switching from a first disease modifying drug (DMD) to cladribine tablets in routine clinical practice at study sites in Italy. The primary objective will be to evaluate changes from baseline in the impact of highly active MS on self-assessed physical functioning 52 weeks after the switch to cladribine tablets using the Multiple Sclerosis Impact Scale-29 (MSIS-29). Secondary objectives will include self-assessed psychological impact of highly active MS in daily life and general health after the switch to cladribine tablets as well as changes in cognitive function, anxiety, and depression symptoms. Additional PRO measures will include the Hospital Anxiety and Depression Scale (HADS), the EuroQoL 5-Dimension 5-Level (EQ-5D-5L), the Work Productivity and Activity Impairment Questionnaire: Multiple Sclerosis (WPAI:MS), and the Patient-Reported Outcomes Measurement Information System (PROMIS). Wearable devices will acquire activity data (step counts, walking speed, time asleep, and energy expenditure). Additional clinical, radiological, and laboratory data will be collected when available during routine management. The findings will complement data from controlled trials by providing insight from daily clinical practice into the effect of cladribine tablets on the patient’s experience and self-assessed impact of treatment on daily life.
Cladribine tablets are a highly effective option for the treatment of relapsingremitting multiple sclerosis (RRMS).
The study aims to evaluate the effectiveness of cladribine in a real-world setting.
...This prospective real-world study consecutively screened all RRMS patients from seven different MS centers in Sicily (Italy) who completed the 2-year treatment course of cladribine tablets in the period between 11
March 2019 and 31
October 2021. Data about Expanded Disability Status Scale (EDSS), relapses, previous treatments, adverse events (AEs) and magnetic resonance imaging (MRI) were collected. Patients who were previously treated with other DMTs were further stratified into moderately active treatment (MAT) and highly active treatment (HAT) patients.
A total of 217 patients (70% women, with a mean age of 38.4 ± 11.3 years) were enrolled. Fifty patients (23.0%) were naïve to treatment and 167 (77%) switched from other disease modifying therapies. After the second year of treatment, about 80% were EDSS progression free, 88% remained relapse-free at T24, and 48% of patients were MRI activity-free. Kaplan Meier analyses showed significant differences between MT and HAT in terms of time to first clinical relapse (HR: 2.43, IC 1.02- 5.76;
= 0.04), time to the first new T1-gadolinium enhancing lesion (HR: 3.43, IC 1.35-8.70;
= 0.009) and time to MRI worsening (HR: 2.42, IC 1.15-5.09;
= 0.02).
This study confirmed that cladribine is an effective treatment for MS, particularly in naïve patients and those who have switched from MATs.
Using flow cytometry, we characterized myeloid, B, and T cells in patients recently diagnosed with relapsing-remitting multiple sclerosis (RRMS) naive to disease-modifying therapies (DMTs).
This ...prospective case-control study was conducted in the tertiary MS center of Catania, Italy. Demographic/clinical data and peripheral bloods were collected from 52 naive patients recently diagnosed with RRMS and sex/age-matched healthy controls (HCs) in a 2:1 ratio. We performed flow cytometry on isolated peripheral blood mononuclear cells to assess immune cell subsets differences between RMMS patients and HCs. We explored the biomarker potential of cell subsets using receiver operating characteristic (ROC) curves and relative area under the curve (AUC) analyses.
Monocytic myeloid-derived suppressor cells (Mo-MDSCs CD14+/HLADR
) and inflammatory monocytes (CD14+CD16+) displayed higher frequencies in RRMS patients when compared with HCs (p <.05). A lower percentage of B-unswitched memory cells was observed in RRMS patients when compared with HCs (p = .026). T cells had a higher frequency of T-helper CD4+ cells and their subset, CD4+CD161+, in RRMS patients when compared with HCs (p <.001). ROC analyses revealed an AUC >70% for Mo-MDSCs CD14+/HLADR
and inflammatory CD14+CD16+, T-helper CD3+CD4+, and T-helper CD4+CD161+.
Patients with a recent RRMS diagnosis and naive to DMTs, showed peculiar myeloid, B-, and T-cell immunophenotypes.
A thinning of intraretinal layers has been previously described in Parkinson's disease (PD) patients compared to healthy controls (HCs). Few studies evaluated the possible correlation between retinal ...thickness and retinal microvascularization. Thus, here we assessed the thickness of retinal layers and microvascular pattern in early PD patients and HCs, using, respectively, spectral-domain optical coherence tomography (SD-OCT) and SD-OCT-angiography (SD-OCT-A), and more interestingly, we evaluated a possible correlation between retinal thickness and microvascular pattern. Patients fulfilling criteria for clinically established/clinically probable PD and HCs were enrolled. Exclusion criteria were any ocular, retinal, and systemic disease impairing the visual system. Retinal vascularization was analyzed using SD-OCT-A, and retinal layer thickness was assessed using SD-OCT. Forty-one eyes from 21 PD patients and 33 eyes from 17 HCs were evaluated. Peripapillary retinal nerve fiber layer (RNFL) and macular RNFL, ganglionic cell layer (GCL), inner plexiform layer (IPL), and inner nuclear layer (INL), resulted to be thinner in PD compared to HCs. Among PD patients, a positive correlation between RNFL, GCL, and IPL thickness and microvascular density was found in the foveal region, also adjusting by age, sex, and, especially, hypertension. Such findings were already present in the early stage of disease and were irrespective of dopaminergic treatment. Thus, the retina might be considered a biomarker of PD and could be a useful instrument for onset and disease progression.
Background: Progressive Multifocal Leukoencephalopathy (PML) is an opportunistic infection caused by John Cunningham virus (JCV) reactivation, potentially associated with natalizumab (NTZ) treatment ...for Multiple Sclerosis (MS). The anti-JCV antibodies titre (JCV index) increases during NTZ treatment; however, the effects of other disease-modifying therapies (DMTs) on the JCV index have not been fully explored. Objective: The aim of the study was to evaluate changes in the JCV index during treatment with several DMTs. Methods: This longitudinal study evaluated the JCV index before starting DMT (T0) and during treatment with DMT (T1). Results: A total of 260 participants (65.4 % females, mean age 43 ± 11.3 ) were enrolled: 68 (26.2 %) treated with fingolimod (FTY), 65 (25 %) rituximab or ocrelizumab (RTX/OCR), 37 (14.2 %) dimethyl-fumarate (DMF), 29 (11.2 %) cladribine (CLD), 23 (8.8 %) teriflunomide (TFM), 20 (7.7 %) interferon or glatiramer acetate (IFN/GA), and 18 (6.9 %) alemtuzumab (ALM). At T1, the percentage of patients with JCV index <0.90 was found to be significantly increased in the ALM group (16.7 % versus 66.7 %, p = 0.05), while the percentage of patients with JCV index >1.51 was found to be significantly reduced in the RTX/OCR group (51.6 % versus 37.5 %, p = 0.04). In the FTY group, a significant reduction in the percentage of patients with JCV index <0.90 was also found (23.5 % versus 1.4 %, p = 0.0006). The mean JCV index was reduced in the RTX/OCR and ALM groups, while a significant increase was observed in the FTY group. Conclusion: DMTs with a T and/or B depleting mechanism of action induced a significant reduction in the JCV index. These results may suggest new possible sequencing strategies potentially maximizing disease control while reducing the PML risk.
Magnetic Resonance Imaging (MRI) techniques provided evidences into the understanding of cognitive impairment (CIm) in Multiple Sclerosis (MS).
To investigate the role of white matter (WM) and gray ...matter (GM) in predicting long-term CIm in a cohort of MS patients.
303 out of 597 patients participating in a previous multicenter clinical-MRI study were enrolled (49.4% were lost at follow-up). The following MRI parameters, expressed as fraction (f) of intracranial volume, were evaluated: cerebrospinal fluid (CSF-f), WM-f, GM-f and abnormal WM (AWM-f), a measure of lesion load. Nine years later, cognitive status was assessed in 241 patients using the Symbol Digit Modalities Test (SDMT), the Semantically Related Word List Test (SRWL), the Modified Card Sorting Test (MCST), and the Paced Auditory Serial Addition Test (PASAT). In particular, being SRWL a memory test, both immediate recall and delayed recall were evaluated. MCST scoring was calculated based on the number of categories, number of perseverative and non-perseverative errors.
AWM-f was predictive of an impaired performance 9 years ahead in SDMT (OR 1.49, CI 1.12-1.97 p = 0.006), PASAT (OR 1.43, CI 1.14-1.80 p = 0.002), SRWL-immediate recall (OR 1.72 CI 1.35-2.20 p<0.001), SRWL-delayed recall (OR 1.61 CI 1.28-2.03 p<0.001), MCST-category (OR 1.52, CI 1.2-1.9 p<0.001), MCST-perseverative error(OR 1.51 CI 1.2-1.9 p = 0.001), MCST-non perseverative error (OR 1.26 CI 1.02-1.55 p = 0.032).
In our large MS cohort, focal WM damage appeared to be the most relevant predictor of the long-term cognitive outcome.
Trends of disease activity during pregnancy, the postpartum period, and until 24 months from the delivery in the era of new drugs for the treatment of relapsing-remitting multiple sclerosis (RRMS) ...need to be investigated.
In this cross-sectional Italian multicenter study, women with RRMS were included; the disease-modifying treatment (DMT) at the time of conception included were: interferons, glatiramer acetate, teriflunomide, dimethyl fumarate, fingolimod, and natalizumab. The main outcome of the study was to determine the rate of relapse occurrence during pregnancy and the postpartum period in all women grouped for each DMT. The secondary outcome was to determine the overall disease activity assessed by NEDA 3 (relapse, disability level, and radiological activity) at 24 months from the date of delivery.
Completed data were available for 81 pregnancies (in 74 women). Women on interferons and glatiramer had longer disease duration than women on dimethyl fumarate, fingolimod, and natalizumab (
< 0.05). Overall, we recorded 25 relapses during pregnancy (11 in 11 women) and the postpartum period (14 in 14 women). Natalizumab was the most commonly DMT in women (3) who experienced relapses during pregnancy. IFNs were the most commonly prescribed DMT in women (8) who experienced relapses during the postpartum period. At logistic regression analysis, specific treatment
was not associated with relapse occurrence. No differences among the DMTs groups were recorded about NEDA 3 status at 24 months of follow-up.
In our population, there was no difference in terms of relapses occurrence, disability status, and the overall disease activity during a follow up of 24 months.
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.
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