Smouldering multiple sclerosis: the ‘real MS’ Giovannoni, Gavin; Popescu, Veronica; Wuerfel, Jens ...
Therapeutic Advances in Neurological Disorders,
01/2022, Letnik:
15
Book Review, Journal Article
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Using a philosophical approach or deductive reasoning, we challenge the dominant clinico-radiological worldview that defines multiple sclerosis (MS) as a focal inflammatory disease of the central ...nervous system (CNS). We provide a range of evidence to argue that the ‘real MS’ is in fact driven primarily by a smouldering pathological disease process. In natural history studies and clinical trials, relapses and focal activity revealed by magnetic resonance imaging (MRI) in MS patients on placebo or on disease-modifying therapies (DMTs) were found to be poor predictors of long-term disease evolution and were dissociated from disability outcomes. In addition, the progressive accumulation of disability in MS can occur independently of relapse activity from early in the disease course. This scenario is underpinned by a more diffuse smouldering pathological process that may affect the entire CNS. Many putative pathological drivers of smouldering MS can be potentially modified by specific therapeutic strategies, an approach that may have major implications for the management of MS patients. We hypothesise that therapeutically targeting a state of ‘no evident inflammatory disease activity’ (NEIDA) cannot sufficiently prevent disability accumulation in MS, meaning that treatment should also focus on other brain and spinal cord pathological processes contributing to the slow loss of neurological function. This should also be complemented with a holistic approach to the management of other systemic disease processes that have been shown to worsen MS outcomes.
Mediterranean coastal dunes are threatened by several factors; particularly, tourism causes modifications to the vegetation and the disappearance of endemic species. Understanding the dunes' ...conservation status is crucial for preserving these vulnerable environments through appropriate management strategies.
This study was conducted on 17 Sardinian coastal dunes, with different levels of touristic pressure. We focused on endemic plant species and developed a new endemicity index (EI).
Our study aimed: 1) to assess the conservation status by applying the diversity indices; 2) to verify if the study sites would reveal a general pattern based on different degrees of human disturbance and 3) to test the effectiveness of the EI index.
Four m2 plots (2 × 2 m) were placed along orthogonal transects to the coastline (446 plots in total), in which all plant species were identified, and their relative abundance was estimated.
We found significant differences among the sites for Hdune and EI values but no statistically significant differences in the N values. The EI showed the high naturalistic value of Sardinian coastal dunes and allowed us to distinguish the sites with higher anthropic pressure.
We found significant differences in the indices among the degrees of human disturbance in the coastal systems. The Hdune values were positively related to a medium level of human disturbance, and the EI allowed us to distinguish the sites with varying levels of human disturbance, although it differentiated better those with the highest anthropic pressure. A medium level of human disturbance was positively related to the plant richness and cover, and human trampling could be tolerated by psammophilous vascular plants.
Results showed a satisfactory conservation status of Sardinian dune systems and highlighted diversity indices as valuable support for implementing a conservation strategy, compatible with the tourism purposes and the integrated management of the Mediterranean coastal dune systems.
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•The new EI index supports the evaluation of coastal dunes' conservation status.•We applied Hdune, Edune and N indices in the Sardinian dune systems.•Plant richness and coverage were recorded in 446 plots placed in 17 coastal dunes.•A medium human disturbance was positively related to the plant richness and cover.•Diversity indices are a support for a conservation strategy compatible with tourism.
An updated inventory of the native vascular flora of Italy, providing details on the occurrence at regional level, is presented. The checklist includes 8195 taxa (6417 species and 1778 subspecies), ...distributed in 1092 genera and 152 families; 23 taxa are lycophytes, 108 ferns and fern allies, 30 gymnosperms and 8034 angiosperms. The taxa currently occurring in Italy are 7483, while 568 taxa have not been confirmed in recent times, 99 are doubtfully occurring in the country and 19 are data deficient. Out of the 568 not confirmed taxa, 26 are considered extinct or possibly extinct.
Background and purpose
There is debate as to whether the apparent rebound after fingolimod discontinuation is related to the discontinuation itself or whether it is due to the natural course of ...highly active multiple sclerosis (MS). Our aim was to survey the prevalence of severe reactivation and rebound after discontinuation of fingolimod in a cohort of Italian patients with MS.
Methods
Patients with relapsing–remitting MS who were treated with fingolimod for at least 6 months and who stopped treatment for reasons that were unrelated to inefficacy were included in the analysis.
Results
A total of 100 patients who had discontinued fingolimod were included in the study. Fourteen patients (14%) had a relapse within 3 months after fingolimod discontinuation, and an additional 12 (12%) had a relapse within 6 months. According to this study's criteria, 10 patients (10%) had a severe reactivation. Amongst these patients, five (5%) had a reactivation that was considered to be a rebound.
Conclusions
The present study showed that more than 26% of patients are at risk of having a relapse within 6 months after fingolimod discontinuation. Nevertheless, the risk of severe reactivations and rebound is lower than has been previously described.
Click here to view the accompanying paper in this volume.
Emerging evidence suggests the prognostic value of spinal cord (SC) pathology in multiple sclerosis (MS). However, the 2021 MAGNIMS-CMSC-NAIMS guidelines don't recommend routine SC MRI for disease ...monitoring. This study investigates the frequency of new asymptomatic and isolated SC lesions, exploring their potential to predict clinical activity and guide treatment decisions.
We enrolled relapsing-remitting MS (RRMS) patients who underwent brain and SC MRI at baseline and after 12 months. New, enlarged, or gadolinium-enhanced (Gd+) lesions on MRI were considered disease activity markers. Clinical relapses and treatment changes observed 3 months after the 12-month MRI were analyzed using regression analysis, evaluating their association with worsening SC findings.
A total of 201 RRMS patients (56 males, 27.9%, mean age 42.5 ± 12.1 years, mean EDSS 2.7 ± 1.9) were included. Isolated worsening of T2 lesion burden in the SC occurred in 16 patients (8%), and 12 (6%) had Gd + lesions. Among patients without brain MRI activity (n = 138), regression analysis revealed a significant association between new Gd + SC lesions and clinical relapses within 3 months of the 12-month MRI (p = 0.024). Worsening SC findings (p = 0.021) and SC lesion enhancement (p = 0.046) emerged as key factors influencing disease-modifying therapy changes within 3 months in these patients. Notably, even without clinical symptoms, worsening SC findings significantly predicted treatment changes (p = 0.003).
Our findings highlight the independent value of SC MRI findings in MS monitoring. Importantly, isolated and asymptomatic SC worsening significantly impacted treatment decisions.
•This study investigated the frequency of new, asymptomatic, and isolated spinal cord (SC) lesions in relapsing-remitting MS (RRMS) patients.•The study aimed to assess the potential of SC lesions for predicting clinical activity and guiding treatment decisions.•This study suggests that SC MRI may aid MS monitoring & treatment decisions beyond brain MRI.
•In the current therapeutic scenario, new drugs are available for patients with progressively active MS.•The review critically analyzes the current measures to assess treatment response in ...progressive MS.•The impact of age and comorbidities on the assessment of MS outcomes is also examined.•A more comprehensive and patient-centered approach to evaluating DMT efficacy is discussed.
New treatment options are available for active progressive multiple sclerosis (MS), including primary and secondary progressive forms. Several pieces of evidence have recently suggested a “window of beneficial treatment opportunities,” principally in the early stages of progression. However, for progressive MS, which is characterised by an inevitable tendency to get worse, it is crucial to redefine the “response to treatment” beyond the concept of “no evidence of disease activity” (NEDA-3), which was initially conceived to evaluate disease outcomes in relapsing-remitting form, albeit it is currently applied to all MS cases in clinical practice. This review examines the current perspectives and limitations in assessing the effectiveness of DMTs and disease outcomes in progressive MS, the current criteria applied in defining the response to DMTs, and the strengths and limitations of clinical scales and tools for evaluating MS evolution and patient perception. Additionally, the impact of age and comorbidities on the assessment of MS outcomes was examined.
• Background and Aims The Mediterranean Basin is one of the most important regions for the Earth's plant biodiversity; however, the scarcity of studies on fine scale patterns of genetic variation in ...this region is striking. Here, an assessment is made of the spatial genetic structure of all known locations of the three Sardinian endemic species of Aquilegia in order to determine the relative roles of gene flow and genetic drift as underlying evolutionary forces canalizing the divergence of Sardinian Aquilegia taxa, and to see if the spatial genetic structure found fits the current taxonomic differentiation of these taxa. • Methods DNA from 89 individuals from all known locations of Aquilegia across Sardinia was analysed by means of amplified fragment length polymorphism (AFLP) markers. Both principal co-ordinates analysis (PCoA) and Bayesian clustering analyses were used to determine the spatial genetic structure irrespective of any taxonomic affiliation. Historical effects of gene flow and genetic drift were assessed by checking for the existence of isolation-by-distance patterns. • Key Results STRUCTURE and PCoA analyses revealed a pattern of genetic variation geographically structured into four spatial genetic groups. No migration-drift equilibrium was detected for Aquilegia in Sardinia, when analysed either as a whole or in individual groups. The scenario approached a Case III pattern sensu Hutchinson and Templeton, which is associated with extreme isolation conditions where genetic drift has historically played a dominant role over gene flow. • Conclusions The pattern of genetic variation of Sardinian taxa of Aquilegia indicates that genetic drift has been historically more influential than gene flow on population structure of Sardinian species of Aquilegia.Limited seed dispersal and divergent selection imposed by habitat conditions have been probably the main causes reinforcing post-Pleistocene geographical isolation of Aquilegia populations. The spatial genetic structure found here is not fully compatible with current taxonomic affiliations of Sardinian Aquilegia taxa. This is probably a consequence of the uncoupling between morphological and genetic patterns of differentiation frequently found in recently radiated taxa.
The relationship between cognitive assessment results in multiple sclerosis (MS) and performance in daily activities (DAs) remains unclear. Our study aimed to evaluate the relationship between ...cognitive functions (CF) measured by tests, performance in DAs, and the perception of CF in patients and their caregivers (CG) in MS.
The Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) battery was used to evaluate cognitive status. We created an ad hoc questionnaire (DaQ) to assess performance in DAs not requiring specific motor skills. We used the Multiple Sclerosis Neuropsychological Questionnaire (MSNQ) to measure each patient self-judgment and caregiver's perception of CF.
Forty-nine patients and their caregivers were included in the study. Significant correlations were found between the BICAMS and the DaQ (Symbol Digit Modalities Test (SDMT): r = - 0.48, p < 0.001; California Verbal Learning Test (CVLT): r = - 0.33, p = 0.01; Brief Visual Memory Test (BVMT-R): r = - 0.42; p = 0.002); patients self-judgment (SDMT: r = - 0.38, p = 0.004; CVLT: r = - 0.26, p = 0.03); caregiver perception of patient's CF (SDMT: r = - 0.52, p < 0.001; CVLT: r = - 0.3, p = 0.01; BVMT-R: r = - 0.42, p = 0.002). The difference in perception between the patients and their caregivers was related to patient age (p = 0.001) and severity of cognitive impairment (p = 0.03).
Cognitive assessment results show a significant correlation with performance in daily activities and with patients and, especially, caregiver perception of cognitive impairment. These data support the importance of a routine evaluation of cognitive function in MS that includes an anamnestic evaluation of patients, and, when possible, consideration of the caregiver's point of view.
The present study aims to describe the evolution of teriflunomide use for multiple sclerosis (MS) in the clinical setting, in particular for naïve patients and young women. Predictors of treatment ...response were also investigated.
This was an independent, retrospective, real-world monocentric study. We analysed the use of teriflunomide from 2016 to 2020 in patients categorized as naïve or switchers, and assessed the variations in its use in men and women by age group. Clinical and MRI data of treated patients were evaluated, and NEDA-3 status at 24 and 36 months was defined. Determinants of therapeutic response were examined using regression analysis.
The study included 319 MS patients exposed to teriflunomide 209 women (65.5%). Of these, 67 (21%) were naïve and 252 (79%) were switchers. A 20% increase of teriflunomide use in the naïve group in the past two years, particularly in 2020, the first year of global Sars-Cov-2 spread, was observed. An increase of teriflunomide use of more than 10% in young women under age 45 was also reported. NEDA-3 status was calculated for 204 patients after 24 months and was achieved in 120 (58.8%) of these ones. NEDA-3 was also achieved in 92/160 (56.8%) patients at 36 months. A lower ARR in the two years prior to teriflunomide treatment (p = 0.026), lower baseline age (p = 0.05), and lower EDSS score (p = 0.009) were associated with achievement of the NEDA-3.
Our study confirms a major evolution in teriflunomide use in clinical settings, particularly for naïve patients and young women.
•Teriflunomide use has progressively increased for treatment of Multiple Sclerosis (MS).•In the last two years, we described a 20% and 10% increase of its use in naïve patients and young women.•The efficacy goal of NEDA-3 at 24 and 36 months was achieved in more than 55% patients.•An adequate shared decision-making process is necessary to identify the best candidate patient.
Phenological studies of medicinal plants have been less explored especially for plants confined in the Himalayan region (India). Here we describe detailed phenological stages of
Megacarpaea polyandra
...Benth.
ex
Madden. This perennial species belongs to the family Brassicaceae and is commonly known as Barmola or Barmau, being a highly valued traditional endemic medicinal plant of Himalaya. Seven principal growth stages from seed germination to senescence as per BBCH (Biologische Bundesanstalt, Bundessortenamt und CHemische Industrie) scale have been described along with secondary growth stages. Barmola exhibited a long juvenile vegetative phase (~ 3 to 4 years) compared to the short reproductive development typical of long-lived semelparous species. The long vegetative phase is characterized by leaf development coupled with an increase in root size. Roots constitute the storage organ from which Barmola translocates resources for development in subsequent periods. At the time of inflorescence emergence (last growth cycle), Barmola root’s reached their maximum size, and the translocation of resources coupled with leaf development sustain the reproductive effort of this species, culminating then with fruit ripening and plant death. The application of the BBCH scale was useful to identify the leaf development phase as the most critical growth stage on Barmola. Future conservation strategies aimed to protect Barmola wild populations should incentive the cultivation of this species to warrant their sustainable use among farmers from the Himalayas.
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