Sars-CoV2 infection in pregnant women with multiple sclerosis.

BACKGROUND: In the general population, maternal SARS-CoV-2 infection during pregnancy is associated with worse maternal outcomes; however, only one study so far has evaluated COVID-19 clinical outcomes in pregnant and postpartum women with multiple sclerosis, showing no higher risk for poor COVID-19 outcomes in these patients. OBJECTIVE: In this multicenter study, we aimed to evaluate COVID-19 clinical outcomes in pregnant patients with multiple sclerosis. METHODS: We recruited 85 pregnant patients with multiple sclerosis who contracted COVID-19 after conception and were prospectively followed-up in Italian and Turkish Centers, in the period 2020-2022. A control group of 1354 women was extracted from the database of the Multiple Sclerosis and COVID-19 (MuSC-19). Univariate and subsequent logistic regression models were fitted to search for risk factors associated with severe COVID-19 course (at least one outcome among hospitalization, intensive care unit [ICU] admission and death). RESULTS: In the multivariable analysis, independent predictors of severe COVID-19 were age, body mass index ⩾ 30, treatment with anti-CD20 and recent use of methylprednisolone. Vaccination before infection was a protective factor. Vaccination before infection was a protective factor. Pregnancy was not a risk nor a protective factor for severe COVID-19 course. CONCLUSION: Our data show no significant increase of severe COVID-19 outcomes in patients with multiple sclerosis who contracted the infection during pregnancy.

The effect of air pollution on COVID-19 severity in a sample of patients with multiple sclerosis.

BACKGROUND AND PURPOSE: Some studies have shown that air pollution, often assessed by thin particulate matter with diameter below 2.5 µg/m3 (PM2.5), may contribute to severe COVID-19 courses, as well as play a role in the onset and evolution of multiple sclerosis (MS). However, the impact of air pollution on COVID-19 has never been explored specifically amongst patients with MS (PwMS). This retrospective observational study aims to explore associations between PM2.5 and COVID-19 severity amongst PwMS. METHODS: Data were retrieved from an Italian web-based platform (MuSC-19) which includes PwMS with COVID-19. PM2.5 2016-2018 average concentrations were provided by the Copernicus Atmospheric Monitoring Service. Italian patients inserted in the platform from 15 January 2020 to 9 April 2021 with a COVID-19 positive test were included. Ordered logistic regression models were used to study associations between PM2.5 and COVID-19 severity. RESULTS: In all, 1087 patients, of whom 13% required hospitalization and 2% were admitted to an intensive care unit or died, were included. Based on the multivariate analysis, higher concentrations of PM2.5 increased the risk of worse COVID-19 course (odds ratio 1.90; p = 0.009). CONCLUSIONS: Even if several other factors explain the unfavourable course of COVID-19 in PwMS, the role of air pollutants must be considered and further investigated.

Signs and symptoms of COVID-19 in patients with multiple sclerosis.

BACKGROUND AND PURPOSE: Clinical outcomes of multiple sclerosis (MS) patients affected by coronavirus disease 2019 (COVID-19) have been thoroughly investigated, but a further analysis on main signs and symptoms and their risk factors still needs attention. The objective of this study was to group together and describe based on similarity the most common signs and symptoms of COVID-19 in MS patients and identify all factors associated with their manifestation. METHOD: Logistic and linear regression models were run to recognize factors associated with each pooled group of symptoms and their total number. RESULTS: From March 2020 to November 2021, data were collected from 1354 MS patients with confirmed infection of COVID-19. Ageusia and anosmia was less frequent in older people (odds ratio [OR] 0.98; p = 0.005) and more in smoker patients (OR 1.39; p = 0.049). Smoke was also associated with an incremental number of symptoms (OR 1.24; p = 0.031), substance abuse (drugs or alcohol), conjunctivitis and rash (OR 5.20; p = 0.042) and the presence of at least one comorbidity with shortness of breath, tachycardia or chest pain (OR 1.24; p = 0.008). Some disease-modifying therapies were associated with greater frequencies of certain COVID-19 symptoms (association between anti-CD20 therapies and increment in the number of concomitant symptoms: OR 1.29; p = 0.05). Differences in frequencies between the three waves were found for flu-like symptoms (G1, p = 0.024), joint or muscle pain (G2, p = 0.013) and ageusia and anosmia (G5, p < 0.001). All cases should be referred to variants up to Delta. CONCLUSION: Several factors along with the choice of specific therapeutic approaches might have a different impact on the occurrence of some COVID-19 symptoms.

Early red nucleus atrophy in relapse-onset multiple sclerosis.

No study has investigated red nucleus (RN) atrophy in multiple sclerosis (MS) despite cerebellum and its connections are elective sites of MS-related pathology. In this study, we explore RN atrophy in early MS phases and its association with cerebellar damage (focal lesions and atrophy) and physical disability. Thirty-seven relapse-onset MS (RMS) patients having mean age of 35.6 ± 8.5 (18-56) years and mean disease duration of 1.1 ± 1.5 (0-5) years, and 36 age- and sex-matched healthy controls (HC) were studied. Cerebellar and RN lesions and volumes were analyzed on 3 T-MRI images. RMS did not differ from HC in cerebellar lobe volumes but significantly differed in both right (107.84 ± 13.95 mm3 vs. 99.37 ± 11.53 mm3 , p = .019) and left (109.71 ± 14.94 mm3 vs. 100.47 ± 15.78 mm3 , p = .020) RN volumes. Cerebellar white matter lesion volume (WMLV) inversely correlated with both right and left RN volumes (r = -.333, p = .004 and r = -.298, p = .010, respectively), while no correlation was detected between RN volumes and mean cortical thickness, cerebellar gray matter lesion volume, and supratentorial WMLV (right RN: r = -.147, p = .216; left RN: r = -.153, p = .196). Right, but not left, RN volume inversely correlated with midbrain WMLV (r = -.310, p = .008), while no correlation was observed between whole brainstem WMLV and either RN volumes (right RN: r = -.164, p = .164; left RN: r = -.64, p = .588). Finally, left RN volume correlated with vermis VIIb (r = .297, p = .011) and right interposed nucleus (r = .249, p = .034) volumes. We observed RN atrophy in early RMS, likely resulting from anterograde axonal degeneration starting in cerebellar and midbrain WML. RN atrophy seems a promising marker of neurodegeneration and/or cerebellar damage in RMS.

Multiple Sclerosis Incidence and Prevalence Trends in the Province of Padua, Northeast Italy, 1965-2018.

BACKGROUND: Previous studies, dating back to the 1960s disclosed a progressive increase in multiple sclerosis (MS) incidence and prevalence in the Province of Padua. To further analyze whether this trend is the effect of the improved diagnostic procedures or is primarily related to a real increase risk of MS, we analyzed MS incidence and prevalence of the 5-year period 2011-2015. METHODS: Patients with a diagnosis of MS or clinically isolated syndrome highly suggestive of MS were included in the study. All available sources of clinical and administrative information were evaluated. Mean annual incidence in the 5-year period 2011-2015 and the prevalence on December 31, 2015 were calculated. RESULTS: The 2011-2015 mean incidence was 6.5/100,000/year, 7.9 for females, 4.1 for males. The overall prevalence was 182/100,000, 241 for females, 116 for males. Compared to the 2000-2009 period, mean age at onset, onset-diagnosis delay and F/M ratio did not significantly change. Since the 1960s, incidence and prevalence of MS linearly increased with no interposed plateau periods. CONCLUSIONS: MS incidence and prevalence further and significantly increased in the period 2011-2015. Our 1965-2015 data indicate a real increased risk of MS and stress a role of exogenous factors in MS susceptibility.

Acute simultaneous development of brain tumour-like lesion and demyelinating polyneuropathy in a patient with chronic relapsing myelitis.

Combined central and peripheral demyelination (CCPD) is a rare chronic inflammatory disorder of the nervous system. We describe the case of a patient with a history of recurrent myelitis that acutely and simultaneously developed a brain tumour-like lesion and a sensitive-motor demyelinating polyneuropathy. The diagnosis of CCPD was supported by a detailed diagnostic workup. Up to date, no similar cases have been reported in the literature.

MRI-detectable cortical lesions in the cerebellum and their clinical relevance in multiple sclerosis.

BACKGROUND: The demonstration of cortical lesions (CL) in the cerebellum by magnetic resonance imaging (MRI) is hampered by technical and anatomical constraints. OBJECTIVE: To investigate the occurrence of cerebellar CL and their correlation with cerebellar-related disability by combining Double Inversion Recovery (DIR) and Phase Sensitive Inversion Recovery (PSIR) MRI images in multiple sclerosis (MS) patients. MATERIAL AND METHODS: 40 MS patients (10 CIS/eRRMS, 24 RRMS, 6 SPMS), having a wide range of disability and disease duration, were enrolled. DIR and PSIR images were obtained with a 3T-MRI. RESULTS: Cerebellar white matter lesions (WML) and/or CL were observed in 33/40 patients (82.5%) among which 14/40 had only CL. CL were demonstrated in 26/40 patients by DIR and in 31/40 by PSIR, and their number increased from CIS/eRRMS to SPMS. PSIR disclosed a significantly higher number of CL compared to DIR (RRMS: p=0.0008; SPMS: p=0.002). CL number correlates with the cerebellar Expanded Disability Status Score (EDSS) score (r=0.72, p<0.0001). No correlation was observed between supra-tentorial and cerebellar CL. CONCLUSIONS: CL are detected by PSIR in the cerebellum of the majority of MS patients, are more than WML, increase with disease progression and strongly correlate with the cerebellar EDSS. Thus, the observation of CL in the cerebellum of MS at clinical onset might be useful for prognostic and therapeutic aims.

Cortical relapses in multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a white and grey matter disease of the central nervous system (CNS). It is recognized that cortical damage (i.e. focal lesions and atrophy) plays a role in determining the accumulation of physical and cognitive disability that is observed in patients with progressive MS. To date, an association of cortical lesions with clinical relapses has not been described. RESULTS: We report clinical and magnetic resonance imaging (MRI) findings of five relapsing-remitting MS (RRMS) patients who had clinical relapses characterized by the acute appearance of cortical symptoms, due to the development of large, snake-like, cortical inflammatory lesions. Symptoms were: acute Wernicke's aphasia mimicking stroke; agraphia with acalculia, not associated to a motor deficit nor linguistic disturbance; hyposthenia of the left arm, followed by muscle twitching of the hand, spreading to arm and face; acute onset of left lower limb paroxysmal hypertonia; and temporal lobe status epilepticus, with psychotic symptoms. CONCLUSIONS: Cortical relapses may occur in MS. MRI examination in MS should include sequences, such as double inversion recovery (DIR) or phase sensitive inversion recovery (PSIR), that are aimed at visualizing cortical lesions, especially in the presence of symptoms of cortical dysfunction. Our observation further stresses and extends the clinical relevance of cortical pathology in MS.

A case of relapsing-remitting tumour-like inflammation of the central nervous system.

The case of a 37-year-old woman suffering from a relapsing-remitting tumefactive inflammatory disease of the central nervous system (CNS) is described. The patient had four severe relapses over eight years, and was treated with steroids, immunosuppression and plasma-exchange with modest benefit. No magnetic resonance imaging or cerebrospinal spinal fluid findings suggestive of multiple sclerosis emerged during the eight-year follow-up. 'Relapsing-remitting tumefactive inflammation' seems to have the features of a distinct inflammatory CNS disease.

The changing clinical course of multiple sclerosis: a matter of gray matter.

OBJECTIVE: Clinical and neuroimaging parameters predictive of the changing clinical course of multiple sclerosis (MS) from relapsing-remitting to secondary progressive have not been clarified yet. We specifically designed a prospective 5-year longitudinal study aimed at assessing demographic, clinical, and magnetic resonance imaging (MRI) parameters that could predict the changing clinical course of MS. METHODS: At study entry and after 5 years, clinical and MRI (ie, gray matter and white matter lesions, including spinal cord lesions, and global and regional cortical thinning) parameters were assessed in a training set of 334 consecutive relapsing-remitting MS patients and in an independent validation set of 84 relapsing-remitting MS patients. RESULTS: Sixty-six (19.7%) relapsing-remitting MS patients changed their clinical course during the study and entered into the secondary progressive phase. Age (p = 0.001, odds ratio [OR] = 1.2), cortical lesion volume (p < 0.001, OR = 1.7), and cerebellar cortical volume (p < 0.001, OR = 0.2) at study entry were found to predict the changing clinical course. The model including only these 3 variables correctly identified 252 of 268 (94.0%) patients who maintained the relapsing-remitting course and 58 of 66 (87.8%) patients who became secondary progressive (cross-validated error rate = 7.2%). When applied on the validation set, the model obtained a similar error rate (8.4%). INTERPRETATION: A prediction model based on age, cortical lesion load, and cerebellar cortical volume suitably explains the probability of relapsing-remitting MS patients evolving into the progressive phase. Gray matter damage appears to play a pivotal role in determining the changing clinical course of MS.

Low degree of cortical pathology is associated with benign course of multiple sclerosis.

BACKGROUND: Although a more favorable course of multiple sclerosis is associated with a low degree of cortical pathology, only longitudinal studies could definitely confirm this association. MATERIALS AND METHODS: We followed 95 early relapsing-remitting MS (RRMS; median Expanded Disability Status Scale (EDSS) = 1.5, mean disease duration = 3.1 ± 1.3 years) and 45 benign MS patients (EDSS ≤ 3.0, disease duration ≥ 15 years, normal cognition) for 6 years, with EDSS evaluations every 6 months and brain magnetic resonance imaging (MRI) at baseline and then yearly. RESULTS: At baseline, we detected 406 cortical lesions (CLs) in 67/95 (70.5%) early RRMS and in 24/45 (53.3%) benign MS patients (p = 0.046). After 6 years, the appearance of new CLs was observed in 80/95 (84.2%; 518 CLs) of our early RRMS and in 25/45 (55.5%; 63 CLs; p < 0.001) benign MS patients. At baseline, after corrections for age and disease duration, we observed a cortical thinning of several frontal and temporal regions in our RRMS study patients, compared to the benign MS patients (p ranging between 0.001-0.05). After 6 years, the cortical thinning had increased significantly in several cortices of RRMS patients, but only in the occipital-temporal (p = 0.036) and superior parietal gyrus (p = 0.035) of those with benign MS. Stepwise regression analysis revealed the CL volume (p = 0.006) and the cortical thickness of the temporal middle (p < 0.001), insular long (p < 0.001), superior frontal (p < 0.001) and middle frontal gyri (p < 0.001) as the most sensitive independent predictors of a favorable disease course. CONCLUSIONS: Our data confirmed that a significantly milder cortical pathology characterizes the most favorable clinical course of MS. Measures of focal and diffuse grey matter should be combined to increase the accuracy in the identification of a benign MS course.

Cortical lesion load associates with progression of disability in multiple sclerosis.

Cortical inflammatory lesions have been correlated with disability and cortical atrophy in multiple sclerosis. The extent to which cortical lesion load is associated with longer-term physical and cognitive disability in different multiple sclerosis phenotypes has not yet been investigated. Thus, a 5-year prospective longitudinal study was carried on in a large group of patients with multiple sclerosis. Three hundred and twelve consecutive patients suffering from multiple sclerosis (157 relapsing remitting, 35 paediatric, 45 benign, 44 primary progressive and 31 secondary progressive) were enrolled in a 5-year prospective clinical and neuroimaging study. Several magnetic resonance parameters (including cortical lesion number and volume, contrast-enhancing cortical lesions and grey matter atrophy) were analysed to find associations with clinical and cognitive outcomes. Patients with high cortical lesion load had higher Expanded Disability Status Scale increase (median = 1.5; range = 0-3) during the study than both patients with low cortical lesion load (median = 1.0; range = 1-3, P < 0.001) and without cortical lesions (median = 0.5; range = -1 to 2, P < 0.001). Compared with clinically stable patients, 101 (32.4%) patients showing clinical progression at 5 years had the highest rate of cortical lesion accumulation (P < 0.001). Stepwise regression analysis revealed significant and independent contributions from age (ß = 0.55), cortical lesion volume (ß = 0.58), T(2) white matter lesion volume (ß = 0.34) and grey matter fraction (ß = 0.42) as predictors (final model with r(2 )= 0.657, P < 0.001) of Expanded Disability Status Scale change. Disease duration (ß = 0.52, P < 0.001), cortical lesion volume (ß = 0.67, P < 0.001), grey matter fraction (ß = 0.56, P < 0.001) and T(2) white matter lesion volume (ß = 0.31, P = 0.040) at baseline were found to be independent predictors of cognitive status at the end of the study. While confirming the relevance of cortical pathology in all multiple sclerosis phenotypes, but benign, our study suggests that grey matter and white matter changes in multiple sclerosis occur, at least, partly independently, and that grey matter, more than white matter, damage is associated with physical and cognitive disability progression. Thus, the combination of grey and white matter parameters gives a more comprehensive view of multiple sclerosis pathology and allows a better understanding of the progressive phase of the disease, which, however, seems more related to cortical damage than to subcortical white matter changes.

Neurodegeneration in the retina of motoneuron diseases: a longitudinal study in amyotrophic lateral sclerosis and Kennedy's disease.

BACKGROUND: To what extent retinal atrophy in neurodegenerative diseases reflects the severity and/or the chronicity of brain pathology or is a local independent phenomenon remains to be clarified. Moreover, whether retinal atrophy has a clinical (diagnostic and prognostic) value in these diseases remains unclear. OBJECTIVE: To add light on the pathological significance and clinical value of retinal atrophy in patients with amyotrophic lateral sclerosis (ALS) and Kennedy's disease (KD). METHODS: Thirty-five ALS, thirty-seven KD, and forty-nine age-matched healthy controls (HC) were included in a one-year longitudinal study. Spectrum-domain optical coherence tomography (OCT) was performed at study entry (T0) and after 12 months (T1). Disease duration and functional rating scale (FRS) for ALS and KD patients were correlated to retinal thicknesses. RESULTS: Compared to HC, peripapillary retinal nerve fiber layer (pRNFL) thickness was significantly thinner in both ALS (p = 0.034) and KD (p = 0.003). pRNFL was thinner in KD compared to ALS, but the difference was not significant. In KD, pRNFL atrophy significantly correlated with both disease severity (r = 0.296, p = 0.035) and disease duration (r = - 0.308, p = 0.013) while no significant correlation was found in ALS (disease severity: r = 0.147, p = 0.238; disease duration: r = - 0.093, p = 0.459). During the follow-up, pRNFL thickness remained stable in KD while significantly decreased in ALS (p = 0.043). CONCLUSIONS: Our study provides evidence of retinal atrophy in both ALS and KD and suggests that retinal thinning is a primary local phenomenon in motoneuron diseases. The clinical value of pRNFL atrophy in KD is worthy of further investigation.

Sexual Dysfunction in Multiple Sclerosis: The Role of Executive Function.

Cognitive impairment and sexual dysfunction are common symptoms in persons with Multiple Sclerosis (MS). The present study focuses on the relationship between these two dimensions by means of a specific assessment commonly used in clinical practice with this population. Fifty-five persons with a diagnosis of MS underwent specific cognitive tests and answered clinical questionnaires. Two cognitive tests, one for memory (the Selective Reminding Test), and one for attention (the Symbol Digit Modalities Test), were administered together with two tests for executive functions (the D-KEFS Sorting Test and Stroop Test). Two self-report questionnaires to investigate clinical, psychological and sexual features (the Beck Depression Inventory-II and Self-perception of Cognition in Multiple Sclerosis and Multiple Sclerosis Intimacy and Sexuality Questionnaire-19), were also administered. The main result highlights that sexual difficulties are associated with cognitive deficits, particularly with executive disorders, but not with memory and attention. Furthermore, sexual difficulties are better explained when depression symptoms are also taken into account. This study disentangles the interaction between sexual dysfunction, cognitive impairment and depression in persons with MS by emphasising the role of very high cognitive processing (i.e., executive functioning) in determining human behaviour.

Clinical Profiles in Multiple Sclerosis: Cognitive Reserve and Motor Impairment along Disease Duration.

(i) Background: Cognitive impairment in people with multiple sclerosis (MS) has been studied in relation to certain clinical variables (e.g., motor disability and disease duration) and lifestyle factors such as cognitive reserve (CR). However, only very few studies have considered the interaction of clinical variables and cognitive reserve in preserving the integrity of the neuropsychological profile. In this paper, we hypothesised that a higher level of CR might predict good cognitive efficiency by modulating the clinical outcome of the disease. (ii) Methods: A sample of 100 participants with MS (age range 30-74), was recruited and assessed remotely with a questionnaire to measure CR and a cognitive screening test. Data were analysed through generalized additive models. (iii) Results: We found that the model analysing the interaction between CR and disease duration, and between CR and motor disability, was able to explain a significant percentage of cognitive performance. In particular, higher levels of CR predicted a better cognitive performance despite a long disease duration, unless the motor disability was severe. (iv) Conclusion: This study highlights the crucial role of CR in modulating cognitive efficiency in people with MS.

Alemtuzumab following natalizumab is more effective in adult-onset than paediatric-onset multiple sclerosis.

Background: Paediatric-onset multiple sclerosis (POMS) therapeutic approach derives from of adult-onset multiple sclerosis (AOMS) tailored algorithms. Objectives: To evaluate in a common clinical scenario the efficacy and safety of alemtuzumab (ALZ) in POMS and AOMS. Methods: All patients switching from natalizumab (NTZ) to ALZ for safety concerns (high anti-John Cunningham Virus Antibody Index value, anti-JCV Index) were enrolled in this single-centre, retrospective, case-control open-label study. Results: Ten POMS and 27 AOMS were followed up for 51.3 months. After month 12, we found a lower risk of clinical or radiological relapses among AOMS patients and among patients with older age at ALZ (both p < 0.05). Survival analysis revealed an increased risk of relapse in POMS compared with AOMS (logrank p = 0.00498) and patients starting ALZ before age 22.75 years than the elder ones (logrank p = 0.0018). Survival analysis did not disclose any difference between AOMS and POMS (logrank p = 0.27) in terms of progression independent of any relapse activity (PIRA). In addition, no evidence of relapse-associated worsening was observed. Autoimmune events were reported by 5 AOMS and no POMS (29.4% versus 0.0%, p = 0.057), and survival analysis was not significant (logrank p = 0.0786). Conclusion: ALZ seems more effective in AOMS than in POMS following NTZ. These findings underrate ALZ effectiveness when shifting from NTZ in POMS.

Patients with multiple sclerosis choose a collaborative role in making treatment decision: results from the Italian multicenter SWITCH study.

BACKGROUND: Clinicians are increasingly recognizing the importance of shared decision-making in complex treatment choices, highlighting the importance of the patient's rationale and motivation for switching therapies. This study aimed to evaluate the association between different modalities of changing multiple sclerosis (MS) treatments, cognitive profile and attitude and preferences of patients concerning treatment choice. METHODS: This multicenter cross-sectional study was conducted at 28 Italian MS centers in the period between June 2016 and June 2017. We screened all MS patients treated with any DMT, with a treatment compliance of at least 80% of therapy administered during the 3 last months who needed to modify MS therapy because of efficacy, safety or other reasons during a follow-up visit. At the time of switching the symbol digit modalities test (SDMT) and the Control Preference Scale (CPS) were evaluated. According to the CPS, patients were classified as "active" (i.e. who prefer making the medical decision themselves), "collaborative" (i.e. who prefer decisions be made jointly with the physician), or "passive" (i.e. who prefer the physician make the decision). RESULTS: Out of 13,657 patients recorded in the log, 409 (3%) changed therapy. Of these, 336 (2.5%) patients, 69.6% were female and with mean age 40.6 ± 10.5 years, were enrolled. According to the CPS score evaluation, a significant high percentage of patients (51.1%) were considered collaborative, 74 patients (22.5%) were passive, and 60 (18.2%) patients were active. Stratifying according to CPS results, we found a higher SDMT score among collaborative patients compared to active and passive ones (45.8 ± 12.3 versus 41.0 ± 13.2 versus 41.7 ± 12.8, p < 0.05). CONCLUSION: In this study, the CPS evaluation showed that more than 50% of patients who needed to change therapy chose a "collaborative" role in making treatment decision. Cognitive profile with SDMT seems to correlate with patients' preference on treatment decision, showing better scores in collaborative patients.