Primary Progressive Form Research Articles

Disclosing the Novel Protective Mechanisms of Ocrelizumab in Multiple Sclerosis: The Role of PKC Beta and Its Down-Stream Targets.

Ocrelizumab (OCR) is a humanized anti-CD20 monoclonal antibody approved for both Relapsing and Primary Progressive forms of Multiple Sclerosis (MS) treatment. OCR is postulated to act via rapid B cell depletion; however, by analogy with other anti-CD20 agents, additional effects can be envisaged, such as on Protein Kinase C (PKC). Hence, this work aims to explore novel potential mechanisms of action of OCR in peripheral blood mononuclear cells from MS patients before and after 12 months of OCR treatment. We first assessed, up-stream, PKCβII and subsequently explored two down-stream pathways: hypoxia-inducible factor 1 alpha (HIF-1α)/vascular endothelial growth factor (VEGF), and human antigen R (HuR)/manganese-dependent superoxide dismutase (MnSOD) and heat shock proteins 70 (HSP70). At baseline, higher levels of PKCβII, HIF-1α, and VEGF were found in MS patients compared to healthy controls (HC); interestingly, the overexpression of this inflammatory cascade was counteracted by OCR treatment. Conversely, at baseline, the content of HuR, MnSOD, and HSP70 was significantly lower in MS patients compared to HC, while OCR administration induced the up-regulation of these neuroprotective pathways. These results enable us to disclose the dual positive action of OCR: anti-inflammatory and neuroprotective. Therefore, in addition to B cell depletion, the effect of OCR on these molecular cascades can contribute to counteracting disease progression.

Insights into refractory chronic inflammatory demyelinating polyneuropathy: a comprehensive real-world study.

Refractory chronic inflammatory demyelinating polyneuropathy (CIDP) is a challenging subset of CIDP. It does not respond well to immune therapy and causes substantial disability. A comprehensive understanding of its clinical profile, electrophysiological characteristics and potential risk factors associated with refractoriness remains to be further elucidated. Data in this cross-sectional study was collected and reviewed from the Huashan Peripheral Neuropathy Database (HSPN). Included patients were categorized into refractory CIDP and non-refractory CIDP groups based on treatment response. The clinical and electrophysiological characteristics were compared between refractory and non-refractory CIDP groups. Potential risk factors associated with refractory CIDP were explored with a multivariate logistic regression model. Fifty-eight patients with CIDP were included. Four disease course patterns of refractory CIDP are described: a relapsing-remitting form, a stable form, a secondary progressive form and a primary progressive form. Compared to non-refractory CIDP patients, refractory CIDP exhibited a longer disease duration (48.96 ± 33.72 vs. 28.33 ± 13.72 months, p = 0.038) and worse functional impairment (MRC sum score, 46.08 ± 12.69 vs. 52.81 ± 7.34, p = 0.018; mRS, 2.76 ± 0.93 vs. 2.33 ± 0.99, p = 0.082; INCAT, 3.68 ± 1.76 vs. 3.03 ± 2.28, p = 0.056, respectively). Electrophysiological studies further revealed greater axonal impairment (4.15 ± 2.0 vs. 5.94 ± 2.77 mv, p = 0.011, ulnar CMAP) and more severe demyelination (5.56 ± 2.86 vs. 4.18 ± 3.71 ms, p = 0.008, ulnar distal latency, 7.94 ± 5.62 vs. 6.52 ± 6.64 ms, p = 0.035, median distal latency; 30.21 ± 12.59 vs. 37.48 ± 12.44 m/s, p = 0.035, median conduction velocity; 58.66 ± 25.73 vs. 42.30 ± 13.77 ms, p = 0.033, median F-wave latency), compared to non-refractory CIDP. Disease duration was shown to be an independent risk factor for refractory CIDP (p < 0.05, 95%CI [0.007, 0.076]). This study provided a comprehensive description of refractory CIDP, addressing its clinical features, classification of clinical course, electrophysiological characteristics, and prognostic factors, effectively elucidating its various aspects. These findings contribute to a better understanding of this challenging subset of CIDP and might be informative for management and treatment strategies.

Sleep disorders in patients with multiple sclerosis in Spain

ObjectiveThis study assesses the presence of sleep disturbances and their relationship with clinical and demographic variables in patients with MS, with a view to establishing correlations between the different variables and the frequency of sleep disturbances. MethodsThe Pittsburgh Sleep Quality Index (PSQI) was used to detect sleep disorders. We contacted patients treated at the MS unit and distributed a questionnaire (PSQI) to 221 patients, receiving 142 usable questionnaires between 8 and 30 September 2019. ResultsThe prevalence of patients with sleep disturbances in our study was 74.7% (73.7% in women and 76.8% in men). Therefore, sleep disorders are pervasive in patients with MS, with 3 out of 4 patients experiencing them, a higher rate than that observed in the population without the disease. The frequency of sleep disorders gradually increased in line with age. In the 2 age groups analyzed, 44–54 years and 55–68 years, the proportion of moderate and severe sleep disorders was 42.8% and 53.9%, respectively. Moderate and severe sleep disturbances were observed in 27.5%, 44.7%, and 58.3% of patients with Expanded Disability Status Scale scores of 0–3, 3–6, and >6, respectively. ConclusionOur results indicate that sleep disorders are more common in patients with MS than in other populations. Patients with secondary progressive forms of MS more frequently present sleep disturbances, while patients with primary progressive forms report them less frequently. Age and degree of disability were positively correlated with the prevalence and severity of sleep disorders in MS patients.

HUMORAL IMMUNITY IN PATIENTS WITH MULTIPLE SCLEROSIS

Introduction. More than 1 million people in the world suffer from multiple sclerosis (MS). The etiology of MS remains not fully understood. The main role in the pathogenesis of MS belongs to the combination of chronic inflammation and neurodegenerative processes, in the genesis of which autoimmune processes play a significant role. Progress in studying the mechanisms of the pathological process of demyelinating diseases has been achieved mainly thanks to immunological research. One of the manifestations of activation of humoral immunity in MS is increased synthesis of immunoglobulins in brain tissue and cerebrospinal fluid&#x0D; The aim of the study. To study the state of humoral immunity in multiple sclerosis patients with different types of disease course&#x0D; Research methods. 68 patients with a verified diagnosis of multiple sclerosis (MS) based on the MacDonald et al criteria aged 19 to 65 years (37 women, 29 men) were examined. The primary progressive type of the course was established in 19 patients, the secondary-progressive - in 3, the remitting-relapsing type of the course - in 26 patients. The control group consisted of 80 practically healthy male volunteers aged 25-45 years.&#x0D; The concentration of immunoglobulins A, G, M in blood serum was determined by the Mancini method (1965). The content of circulating immune complexes (CIC) in blood serum was determined by the method of precipitation in polyethylene glycol.&#x0D; Results and discussion. The highest content of Ig A was observed in the group of patients with primary progressive form of MS, which was 3.7 times higher than normal values and 1.2 times higher than in the general group of MS patients. In the group of patients with the secondary progressive form of MS, the content of Ig A was 3.1 times higher than in the control group and 1.2 times lower than in the group with the primary progressive form. In the group of patients with relapsing-remitting form of MS, there was an increase in the level of Ig A three times relative to the normal indicator, and a decrease (by 1.2 times) relative to the level in the group with a primary progressive form of MS.&#x0D; The content of Ig M in the blood serum of patients with MS exceeded the norm by 5 times. In the group with the primary progressive form of MS, the level of Ig M was 3.5 times higher than the level in the control group and 1.5 times lower than the level in the group of patients with MS. In patients with secondary progressive form of MS, the content of Ig M was 2.6 times higher than the norm, but 1.3 times lower than the level in the group with primary progressive form of MS and 1.9 times lower than in the group of patients with MS. In patients with the relapsing-remitting form of MS, the level of Ig M was: 4.6 times higher than the level in the control group and 1.7 times higher than the content in patients with the secondary-progressive form of MS, and also 1.3 times higher, than in the group with the primary progressive form.&#x0D; In all groups of patients with MS with different types of the course of the disease, the most pronounced increase in the level of Ig G was noted.&#x0D; The highest level of CIC was recorded in the general group of patients with MS and in the group with secondary progressive form of MS.&#x0D; Conclusions. An imbalance of the humoral link of immunity was observed in patients with multiple sclerosis. A probable increase in the concentration of Ig A in the blood serum of patients with multiple sclerosis indicates the presence of infection of the mucous membranes, which is especially pronounced in patients with the primary progressive form of multiple sclerosis. A significant increase in the content of Ig G in the blood serum of patients with multiple sclerosis indicates a chronic course of the process, which is especially evident in the relapsing-relapsing form of multiple sclerosis. An increased concentration of IgM in the blood serum of patients with multiple sclerosis may indicate an exacerbation of the course of chronic inflammation, especially in the case of relapsing-remitting multiple sclerosis. The detected fluctuations of the average content of CIC in the blood serum of patients with multiple sclerosis did not go beyond the physiological norm.

The role of ocrelizumab in recommendations and in the Polish therapeutic programme

Multiple sclerosis is a heterogeneous and chronic disease, and the primary goal of treatment is to prevent relapses and slow the progression of disability. Ocrelizumab is a generally well-tolerated disease-modifying therapy for multiple sclerosis, with high efficacy in the treatment of active relapsing forms, and a valuable treatment method for delaying the progression of the disease in patients with the primary progressive form. The activity of relapsing multiple sclerosis is defined on the basis of the clinical course of the disease or radiological findings assessed over a year. The occurrence of clinical relapses and/or activity on magnetic resonance imaging is taken into account. In line with the recommendations of the European Committee for Treatment and Research in Multiple Sclerosis and the European Academy of Neurology, as well as in accordance with the guidelines of the American Academy of Neurology, updated in 2021, depending on the disease activity in the early stage of multiple sclerosis, the choice of a disease-modifying drug should be motivated by higher efficacy. Recommendations for the treatment of multiple sclerosis in most countries in Europe and around the world are based on the above-mentioned guidelines. In Poland, recommendations for treatment modifying the course of multiple sclerosis were developed in 2023 by experts from the Multiple Sclerosis and Neuroimmunology Section of the Polish Neurological Society. Treatment based on the B.29 drug programme of the National Health Fund in Poland allows, from 1 July 2023, in addition to escalation, using the induction model based on highly effective therapies as first-line treatment.

Why do we so rarely recognise and treat the primary progressive form of multiple sclerosis?

The primary progressive form of multiple sclerosis is characterised by a systematic increase in disability from the onset of the disease, usually without overlapping relapses. It is estimated that it accounts for 10–15% of all cases of multiple sclerosis, occurs with similar frequency in both sexes, and its symptoms appear at an older age, usually after 40. The initial manifestation usually consists of pyramidal symptoms and myelopathy. The most typical symptoms include progressive gait and sphincter function impairment. Symptoms of cerebellar syndrome, truncal syndromes, as well as visual and cognitive disturbances are less common. The clinical course with characteristic symptomatology resulting from the location of the changes primarily in the spinal cord, followed by the occurrence of initial symptoms, means that this form of multiple sclerosis requires careful differential diagnosis. It should be differentiated primarily from diseases causing lower limb paresis (myelopathy associated with vitamin B12 deficiency, amyotrophic lateral sclerosis, spinal cerebellar ataxia, neuromyelitis optica spectrum disorder, Wernicke’s encephalopathy, Lyme disease, and spinal cord tumours). The diagnosis of primary progressive multiple sclerosis should be guided by the current 2017 McDonald diagnostic criteria. Understanding these criteria and being aware of the differences from the most common relapsing-remitting form of multiple sclerosis can be helpful in speeding up the diagnosis and implementing effective treatment. Even though new treatment options have emerged in recent years, primary progressive multiple sclerosis is still little known and too rarely recognised.

OPERA and ORATORIO – how the world has been changed by “music”

Multiple sclerosis is a chronic autoimmune disease that progresses over time, leading to disability. The condition is still incurable, but available therapies are increasingly effective. Ocrelizumab is the first anti-CD20 monoclonal antibody approved for the treatment of relapsing-remitting and primary progressive forms of multiple sclerosis. In the article, based on the results of the OPERA and ORATORIO clinical trials, their extensions, and post-hoc and meta-analyses, the evidence for long-term high effectiveness of the molecule is presented. Aspects including the control of relapses (annual relapse rate and time to relapse), delay in the occurrence of confirmed disability, probability to achieve disability improvement, need to use a wheelchair and loss of upper limb mobility, as well as radiological activity (gadolinium-enhancing lesions, new T2 lesions, brain atrophy), are assessed. An additional advantage of the OPERA studies is that almost similar results, acquired with identical protocols in a different patient populations, were achieved. Moreover, the effects of therapy did not wear off over time. Based on these findings, ocrelizumab can be regarded as a highly effective therapy in multiple sclerosis, with the highest (48%) NEDA-3 index (no evidence of disease activity) and the greatest potential for delaying the onset of confirmed disability. The presented studies also confirm the benefit of introducing the drug in multiple sclerosis therapy as early as possible.

Real world study of ocrelizumab in multiple sclerosis: Kuwait experience

BackgroundOcrelizumab is a humanized anti-CD20 antibody that has been approved for the treatment of patients with multiple sclerosis (MS). Real-world data in the Middle East is very limited. ObjectivesTo describe the effectiveness and safety of ocrelizumab treatment in MS patients in a real clinical setting. MethodsThis is an observational, registry-based study. MS patients who were treated with ocrelizumab and completed at least one-year follow-up post-treatment were included. Baseline clinical and radiological characteristics were collected before ocrelizumab initiation. The relapse rate, disability measures, magnetic resonance image (MRI) activity (new T2 lesions and/or GD+ enhancing T1 lesions), and adverse events (AE) at the last follow-up visits were assessed. ResultsData from 447 patients were analyzed, of which 260 (58.2%) were females. The mean age and mean disease duration were 37.39 ± 11.61 and 9.38 ± 7.57 years respectively. Most of the cohort was of a relapsing form (74.3%; n = 332), whereas active secondary and primary progressive forms represented 15.4% (n = 69) and 10.3% (n = 46) respectively. In the relapsing cohort, Ocrelizumab was prescribed in 162 (48.8%) patients due to highly active disease, and in 99 (29.8%) patients due to disease breakthrough while on prior therapies. In the last follow-up visits, most of the relapsing cohort was relapse-free (95.8% vs. 27.4%; p <0.001), had no evidence of MRI activity (3.6% vs. 67.5%; p <0.001) while EDSS score was stable (1.80+1.22 vs. 1.87+1.16; p < 0.104) when compared to baseline. NEDA-3 was achieved in 302 (91%) of RRMS patients. Confirmed disability progression was 27.5% and 23.9% in SPMS and PPMS respectively. Adverse events were observed in 139 (31.1%); infusion reactions and infections represented the most. ConclusionThis study showed that ocrelizumab is an effective and safe treatment for MS patients in a real clinical setting similar to what was observed in clinical trials.

How to measure the treatment response in progressive multiple sclerosis: Current perspectives and limitations in clinical settings'.

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.

The therapeutic value of treatment for multiple sclerosis: analysis of health technology assessments of three European countries.

In accordance with European regulation, medicines containing a new active substance to treat neurodegenerative diseases as well as autoimmune and other immune dysfunctions must be approved by the European Medicines Agency (EMA) through the centralized procedure before they can be marketed. However, after EMA approval, each country is responsible for national market access, following the assessment performed by health technology assessment (HTA) bodies with regard to the therapeutic value. This study aims to provide a comparative analysis of HTA recommendations issued by three EU countries (France, Germany, and Italy) for new drugs for multiple sclerosis (MS) following EMA approval. In the reference period, we identified 11 medicines authorized in Europe for MS, including relapsing forms of MS (RMS; n = 4), relapsing-remitting MS (RRMS; n = 6), secondary progressive MS (SPMS; n = 1), and the primary progressive form (PPMS; n = 1). We found no agreement on the therapeutic value (in particular, the "added value" compared to the standard of care) of the selected drugs. Most evaluations resulted in the lowest score ("additional benefit not proven/no clinical improvement"), underlining the need for new molecules with better efficacy and safety profiles for MS, especially for some forms and clinical settings.

Overactive bladder and multiple sclerosis in the University Hospital of Oujda

BackgroundMultiple sclerosis (MS) is the most frequent autoimmune neurological disease in the young population. Vesico-sphincter disorders are frequent in the course of the disease; it has been reported that 90% of MS patients will develop a lower urinary tract disorder within 18 years of the diagnosis.MethodsThe aim of this study is to identify the frequency, severity, diagnosis, and treatment of overactive bladder (OAB) in MS patients at the Mohammed VI hospital university in Oujda-Morocco. It is a cross-sectional study. The population was collected in neurology department of Mohammed VI hospital university in Oujda-Morocco. The population cohort consisted of patients diagnosed with multiple sclerosis, which were invited to the urology department where they underwent urinary screening and completed a form of questions regarding the frequency and severity of OAB and its influence on quality of life.ResultIn our study, the mean age of the patients was 43 years, and our sample was composed of 48% males and 52% females, and the most frequent lower urinary tract symptom was urgency (57%), followed by urinary frequency (29%) and urge incontinence (14%). The recurrent-remittent form was the most frequent (62%), followed by the primary progressive form (24%) and the secondary progressive recurrent form (14%). Among the patients, 33% presented a mild symptomatology, 48% moderate, and 19% severe. In this study, it was found that the intensity of urinary symptoms and the MS disability score were positively correlated with quality of life and disease duration.ConclusionThe urgency was the major symptom of the lower urinary tract, and the MS disability score and the severity of OAB were associated with the quality of life of the patients. The urological evaluation of patients with multiple sclerosis should be performed routinely to identify OAB and to treat this condition appropriately.

Impact of multiple sclerosis on mental health: A Cross-Sectional Study

IntroductionWhen we think of multiple sclerosis (MS), we usually talk about the sensory and motor symptoms of the disease and their impact on the functioning of the individual affected. However, this disability can lead to a wide range of symptoms, including psychological and cognitive manifestations that also have a significant impact on the quality of life of patientsObjectivesTo estimate the incidence of psychiatric disorders in patients with MS.MethodsA cross-sectional descriptive study that interested MS patients referred to the occupational pathology consultation of the Charles Nicolle Hospital, during the period from July 1, 2020, to September 30, 2022. The data collected concerned the characteristics of the disease. The detection of psychiatric disorders was studied through a validated self-questionnaire GHQ-12 (General Health Questionnaire).ResultsThe study population consisted of 26 cases. The average age was 38 ± 9 years. A predominance of females was noted in 77% of cases. Eight patients (31%) were smokers. Nine cases (47%) had a relapsing-remitting form and six cases (32%) had a primary progressive form. All patients were on disease-modifying therapy. The average duration of the disease was 6 ± 3 years. The average duration of work during the illness was 4 years [one year-12 years]. The average duration of work stoppage in the last 12 months of activity was 63 days [2-240 days], of which 54% was long-term sick leave. The mean GHQ-12 score was 4.38 [0-10]. Twenty patients (77%) had psychological disorders.ConclusionsThis study shows the high frequency of psychiatric disorders in our MS patients. The role of the neuropsychologist is therefore often crucial in the care of these patients.Disclosure of InterestNone Declared

Anti-CD20 immunotherapy in progressive multiple sclerosis: 2-year real-world follow-up of 108 patients.

Anti-CD20 monoclonal antibodies are recently introduced treatments in progressive MS and real-world data are lacking. The aim of this study is to describe a cohort of progressive MS patients treated with ocrelizumab or rituximab in a real-world setting. This monocentric prospective cohort study at the University Hospital of Strasbourg included patients with primary progressive or secondary progressive MS that started treatment with anti-CD20 antibodies before June 2019. Every six months, patients were assessed using the following standardized clinical evaluations: Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW), 9-Hole Peg Test (9-HPT) and Symbol Digit Modalities Test (SDMT). The primary analysis considered EDSS progression (of at least 1.0 if EDSS ≤ 5.5 and at least 0.5 if EDSS ≥ 6.0). We included 108 patients, with a median age upon inclusion of 53years [48.0-58.0]. 72% were classified as primary progressive forms. Median baseline EDSS was 6.0 [4.0-6.5]. EDSS was significantly correlated with T25FW, SDMT and 9-HPT. Following 2years of treatment, 38.9% of patients presented EDSS progression compared to baseline. Our large cohort confirms tolerance of these treatments in a real-world setting. Standardized clinical assessments could improve detection of deteriorating patients. Further studies are needed to establish predictive factors.

Effectiveness of Anti-Cluster of Differentiation 20 as a Disease-Modifying Therapy in Multiple Sclerosis Across Its Different Phenotypes at the University Hospital of Caen.

BackgroundMultiple sclerosis is a chronic, demyelinating disorder occurring primarily as two main forms of relapsing-remitting multiple sclerosis (RRMS) found predominantly in women, and primary progressive multiple sclerosis (PPMS) occurring predominantly in men. In this retrospective single-center study, we aimed to explore the effects of anti-cluster of differentiation (CD)20 treatment for both relapsing-remitting and primary progressive forms of multiple sclerosis (MS) in a population-based cohort treated at the university hospital. MethodologyThe diagnostic factors being assessed were forms of multiple sclerosis (MS), age at first relapse, whereas therapeutic factors were age at first disease-modifying therapy (DMT), age at starting anti-CD20, reason to switch to anti-CD20 and the duration of anti-CD20 treatment. Primary outcomes measured were number of relapses and progression in disability as measured by the Expanded Disability Status Scale, while secondary outcomes measures being assessed number of cerebral lesions on MRI and level of IgG at the beginning and end of the 12-month treatment.ResultsTreatment with anti-CD20 demonstrated a reduction in number of relapses 12 months after treatment, no change in the progression of disability in RRMS type, but an increase in PPMS type. No change was observed in cerebral MRI lesions at the end of treatment after 12 months. A statistically significant reduction in serum IgG value was observed after 12 months from the start of treatment, where only one out of 26 (3.8%) patients developed hypogammaglobulinemia with IgG less than 6 g/L but none developed hypogammaglobulinemia of less than 5 g/L.ConclusionAnti-CD20 antibodies as disease-modifying therapy can profoundly impact the course and progression of MS in both its forms if utilized at an earlier stage in patients and therefore greatly improve the quality of life in patients living with multiple sclerosis.

Evaluation of corneal sensitivity in multiple sclerosis patients.

Purpose:To measure the corneal sensitivity in patients with multiple sclerosis (MS), to compare it with normal values and to study its correlation with different disease characteristics.Methods:Corneal sensitivity of 28 MS patients was compared to corneal sensitivity of 28 age- and gender-matched normal controls. Corneal sensitivity was measured using the Cochet-Bonnet esthesiometer and was correlated to the duration, type and severity indexes of the disease.Results:Corneal sensitivity was comparable between both groups (P = 0.79). No statistically significant correlation was found between corneal sensitivity and the duration of MS (P = 0.55) nor the severity indexes of MS (expanded disability status scale [EDSS] P = 0.52, global multiple sclerosis severity score [MSSS] P = 0.64). Following subgroup analysis, only the primary progressive (PPMS) form of MS had a reduced corneal sensitivity with P = 0.023, while remittent-recurrent (RRMS), secondary progressive (SPMS), and clinically isolated (CIS) forms of MS did not have any reduction in the corneal sensitivity. “ROC curve analysis” showed an area under the curve of 0.48.Conclusion:In the exception of PPMS subtype, MS patients have similar corneal sensitivity in comparison to controls. Cochet-Bonnet esthesiometer does not seem to be a good diagnostic tool or a disease severity marker for patients with MS.

Modifications to the “Classical” Autologous Hematopoietic Stem Cell Transplantation in Multiple Sclerosis: Efficacy and Safety Study of a Less Toxic Approach Which Improves the Neurological Condition. a Mexican Perspective

Background: In an effort to reset the immune system, patients with multiple sclerosis (MS) have been autografted with stem cells; we have shown that these grafts can be performed on an outpatient basis with non-frozen peripheral blood hematopoietic stem cells (PBSC) and a conditioning regimen of cyclophosphamide (Cy) and rituximab, the so-called “Mexican method”.Material and methods: Since 2015, all consecutive patients with MS were autografted in two centers in Mexico, following the “Mexican method” (ClinicalTrials.gov identifier NCT02674217), on an outpatient basis and employing PBSC. Mobilization was accomplished with Cy and filgrastim (G-CSF); cumulative dose of Cy was 200 mg/kg. Cy doses were delivered in two separate blocks nine days apart, with the initial aim of mobilizing PBSC and purging lymphoid cells, while the second further purged lymphoid cells and conditioned the graft. After granulocyte recovery, patients were administered rituximab (375 mg/m2) and again (100 mg) every two months, over a 12-mo. period. The extended disability status scale (EDSS) score was assessed every 3 mos. after transplant.Results: 392 patients were autografted; median age was 47 years; time to neutrophil recovery > 0.5 x109/L was 7 days (0-12). The outpatient procedure was completed in 382 patients (97.4%); 10 patients were admitted to the hospital due to neutropenic fever (2), persistent nausea / vomiting (2), iatrogenic pneumothorax (4) and dehydration (2). Transplant related mortality was zero. The 12-mo. progression-free survival was 75%. Improvement or stabilization of the EDSS score at 12 mos. was observed in 75, 72 and 60% of patients with relapsing remitting (RR), secondary progressive (SP) or primary progressive (PP) forms of MS. In patients with a response, EDSS values decreased significantly from 4.83 ± 0.21 to 3.49 ± 0.24 three mo. after grafting (p = 0.007) and from 4.39 ± 0.49 to 3.32 ± 0.50 twelve mo. after grafting (p = 0.05).Conclusions: The Mexican autograft method in MS carries a very low morbidity and no mortality, induces neurological responses in MS, even in variants in which other autograft protocols have not proven useful, such as SP-MS and PP-MS. Additional information and follow-up is needed to further support these observations. DisclosuresGomez-Almaguer:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bristol: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees.

Sleep disorders in patients with multiple sclerosis in Spain

ObjectiveThis study assesses the presence of sleep disturbances and their relationship with clinical and demographic variables in patients with MS, with a view to establishing correlations between the different variables and the frequency of sleep disturbances. MethodsThe Pittsburgh Sleep Quality Index (PSQI) was used to detect sleep disorders. We contacted patients treated at the MS unit and distributed a questionnaire (PSQI) to 221 patients, receiving 142 usable questionnaires between 8 and 30 September 2019. ResultsThe prevalence of patients with sleep disturbances in our study was 74.7% (73.7% in women and 76.8% in men). Therefore, sleep disorders are pervasive in patients with MS, with 3 out of 4 patients experiencing them, a higher rate than that observed in the population without the disease. The frequency of sleep disorders gradually increased in line with age. In the 2 age groups analyzed, 44–54 years and 55–68 years, the proportion of moderate and severe sleep disorders was 42.8% and 53.9%, respectively. Moderate and severe sleep disturbances were observed in 27.5%, 44.7%, and 58.3% of patients with Expanded Disability Status Scale scores of 0–3, 3–6, and >6, respectively. ConclusionOur results indicate that sleep disorders are more common in patients with MS than in other populations. Patients with secondary progressive forms of MS more frequently present sleep disturbances, while patients with primary progressive forms report them less frequently. Age and degree of disability were positively correlated with the prevalence and severity of sleep disorders in MS patients.

Real-world experience of ocrelizumab initiation in a diverse multiple sclerosis population

BackgroundOcrelizumab (OCR) is a humanized monoclonal antibody directed against CD20 positive B-lymphocytes. It was approved for use in 2017 by the U.S. Food and Drug Administration (FDA) for both the relapsing-remitting and primary progressive forms of multiple sclerosis (MS). ObjectiveTo provide real-world data for patients with MS treated with OCR in our center and evaluate both the safety and efficacy across different ethnic groups not studied in previous clinical trials. MethodsWe performed a retrospective observational analysis of MS patients who were treated with OCR from March 31, 2017 to April 30, 2020. We collected data on patients who had received at least a one dose infusion of OCR at our MS center. Patient characteristics, including demographics, clinical disease course, and documented side effects, were collected and analyzed. ResultsA total of 82 patients were eligible for this study, of which 72% had relapsing-remitting MS (RRMS), 14% had primary progressive MS (PPMS), and 11% active/relapsing secondary progressive MS (SPMS). 22% of our patients were of African American descent, 61% Caucasian, and 17% of Hispanic descent. The mean age of starting OCR was 41 ± 11 years. 47% were treatment naïve when started on OCR, 24% were previously treated with one disease-modifying therapy (DMT), 14% were treated with two DMTs, and 15% were treated with more than two DMTs prior to OCR. 50% of patients had at least one adverse event while on OCR; 4.8% had adverse events requiring to OCR discontinuation, 36% had infusion-related reactions, and 7.3% had viral infections. We found two cases of severe babesiosis along with index cases of re-activation of lichen planus, agranulocytosis, severe lymphopenia, and ectopic pregnancy. There were no cases of malignancy, progressive multifocal leukoencephalopathy, or death within our cohort. The mean time after OCR initiation was 17.3 months in the RRMS group, 22.2 months in the PPMS group, and 28.2 months in SPMS group. The annualized relapse rate reduced from 1.33 to 0.15 in the RRMS group. The mean extended disability status scale (EDSS) scores did not worsen across MS phenotypes and ethnic groups while being treated with OCR. ConclusionsIn a diverse patient population, OCR was well-tolerated without significant adverse events. There were novel cases of severe babesiosis, re-activation of lichen planus, lymphopenia, agranulocytosis, and ectopic pregnancy. It is vital to consider geographic risk factors that may expose patients to Babesia microti (B. microti) when either considering or initiating OCR therapy. There were an additional six cases of severe B. microti cases associated with OCR that were reported to the FDA adverse event reporting system (FAERS) along with multiple babesiosis cases associated with other DMTs, including rituximab. OCR was found in our cohort to be effective by decreasing relapse rates and maintaining EDSS scores. Our study extends the generalizability of OCR from clinical trials to a real-world setting consisting of a diverse population.

Ocrelizumab as a breakthrogh in multiple sclerosis treatment

Multiple sclerosis is the most commonly occurring inflammatory disease of the nervous system. It is estimated that over 2 million people suffer from this disease. Currently SM is untreatable, one can only try to stop the progression of the disease or reduce severity of the symptoms. There have been numerous studies on the effectiveness of other monoclonal antibodies in the treatment of multiple sclerosis. A drug that offers a chance for a breakthrough in the treatment of multiple sclerosis is ocrelizumab. It is a monoclonal antibody directed against B lymphocytes expressing the CD20 antigen. Results of the studie confirm the efficacy of ocrelizumab in inhibiting ongoing nerve fiber degeneration and reducing the inflammation associated with it, as well as the near complete depletion of CD20+ B lymphocytes and partial depletion of CD20+ T lymphocytes. They also suggest that ocrelizumab is a safe and effective treatment for multiple sclerosis.Studies conducted on the therapeutic efficacy of ocrelizumab show that its effect on disease progression is superior compared to some current drugs. Ocrelizumab also has a similar safety profile to the currently used interferon β-1a. An important feature of ocrelizumab is its efficacy in the treatment of the primary progressive form of MS, where significant therapeutic efficacy with other drugs has not been seen to date.

Homonymous visual field defects in patients with multiple sclerosis: results of computerised perimetry and optical coherence tomography.

Visual dysfunction is frequent in multiple sclerosis, usually resulting from retrobulbar optic neuritis or papillitis. Less frequently, demyelinating lesions can affect the retrochiasmal pathways. There are few reports of homonymous visual field defects (HVFD) in multiple sclerosis and little is known about their evolution. The purpose of this study was to better define both the clinical profile and the evolution of HVFD in patients with multiple sclerosis. We performed a retrospective study of all multiple sclerosis patients who presented HVFD and were examined by automated static perimetry. A subset of patients benefited from macular assessment with optical coherence tomography (OCT). We also reviewed the worldwide literature on the subject. Twenty patients were retrieved from the neuro-ophthalmology database of the H&ocirc;pital Ophtalmique Jules-Gonin. There were 11 women and 9 men, and their average age was 35 &plusmn; 11 years. The relapsing-remitting form of multiple sclerosis was most common (18/20; 90%), the primary progressive form (1/20; 5%) and the secondary progressive form (1/20; 5%) were rare. HVFD were the presenting symptom of multiple sclerosis in seven patients (35%). The recovery was complete in 12/20 patients (60%), and the median time to recovery was 10 weeks (2-13 weeks). An incomplete recovery was found in 5/20 subjects (25%) and no recovery occurred in 3/20 subjects (15%). Magnetic resonance imaging disclosed a definite lesion explaining the HVFD in 7/11 patients: five within the optic radiations (71.4%), one within the optic tract (14.3%) and one within the lateral geniculate nucleus (14.3%). Our results were comparable to those compiled from our literature search (29 publications, totalling 70 cases). A recurrent episode of HVFD occurred in three patients (15%). OCT was performed in 10/20 patients. Retinal ganglion cell layer thickness was assessed and revealed a homonymous thinning in three patients, diffuse unilateral or bilateral thinning (resulting from previous episodes of optic neuritis) in six patients, and normal retinal ganglion cell layer thickness in one patient. HVFD in multiple sclerosis are found mostly in young patients with relapsing-remitting multiple sclerosis, which is consistent with the epidemiology of multiple sclerosis. HVFD can be the first manifestation of multiple sclerosis and have a relatively good prognosis. Like optic neuritis, HVFD can recur. The incidence of HVFD in multiple sclerosis is unknown, as it is probably underdiagnosed. Systematic automated static perimetry and OCT could help to determine the true incidence of HVFD in multiple sclerosis. &nbsp.