Impact of rituximab in Mexican patients with Multiple Sclerosis-A single-center retrospective study.

BACKGROUND: Multiple Sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS). B cells have an essential role in the disease pathogenesis and therefore selective B-cell depletion are commonly used to treat the disease. Rituximab (RTX), a chimeric anti-CD20 monoclonal antibody had demonstrated reduced inflammatory activity and radiological activity in MS patients. Due to economic constrains and treatment access limitations, RTX is often used as a treatment alternative in these patients. Here, we described our center experience in RTX -treated MS patients. METHODS: A single-center observational retrospective study was conducted in a Mexican cohort MS during 2010 to 2020. All patients had a confirmed MS diagnosis.All patients received fixed scheme involving induction with 1 g on day one and day 15, followed by 500 mg-1 g every six months for maintenance. Annual Relapse Rate (ARR), Progression index (PI), Expanded Disability Status Scale (EDSS) and MRI activity of the disease were evaluated. Comparison between naïve and non-naïve patients was also conducted. RESULTS: A total of 85 patients were included. The mean age at diagnosis was 33.13 (±8.90) years with 73 (85.9%) being RRMS. 39 (34.1%) were treatment-naïve. While treated with RTX, 62(72.9%) patients reached a free-of-relapse status, with statistically significant decrease in the mean ARR from 0.82 to 0.36 [0.14 (95%CI: 0.09-0.20), p = 0.0001 and EDSS [0.25 CI 0-0.5 (p = 0.034)] and a decrease in their T1 Gd-enhancing MRI lesions (1.64 vs. 0.12 CI 0.70-2.30, p = 0.004. 29 (29.4%) patients achieved NEDA-3. Among all patients, only 2 (2.4%) experienced infusion-related mild adverse events. No serious adverse events were reported. CONCLUSION: We found significant clinical and radiological improvement in naïve and non-naïve MS patients treated with RTX.

Optic neuritis after COVID-19 vaccine application.

As the COVID-19 pandemic continues to rise, the development of effective vaccines is of crucial importance to prevent further morbidity and mortality. In parallel, some rare adverse events related to COVID-19 vaccines, have been reported, most of them mild. Here we report the case of a previously healthy 19-year-old woman who developed optic neuritis 1 week after single dose of Ad26.COV2.S vaccine with marked improvement after management with steroids. Although causality cannot be confirmed due to lack of a biological marker, this case may help to guide further research for potential pathogenic mechanism.

Brain MRI volumetric changes in the follow-up of patients with anti-NMDAr encephalitis.

INTRODUCTION: Autoimmune anti-NMDAr encephalitis is an antibody-mediated disorder characterized by psychiatric symptoms followed by decreased consciousness, dysautonomia and seizures. The pathophysiology of the disease is related to the internalization of NR1 subtype NMDA receptors and the dysfunction of structures where they are abundant (frontotemporal and insular regions). Some reports suggest the existence of cerebral atrophy in the follow-up of these patients, with conflicting evidence regarding its presence and usefulness as a marker of prognosis. METHODS: In a longitudinal, observational study, all patients with the diagnosis of definite anti-NMDAr autoimmune encephalitis with initial and control MRI studies were included. Conventional MR Brain acquisition was performed using a 3-Tesla Skyra MRI System. Automated brain segmental analysis was performed using the Volbrain volumetry system. The differences between baseline MRI volumetric characteristics and volumetric measures at follow-up was assessed. RESULTS: 25 patients were included (mean age 26.6, SD 9.6). 44% were females. The mean time between the studies was 24 (SD 21.4, 3-24) months. Significant volume loss was identified in the total brain volume (- 0.02%, p = 0.029), cerebellar volume (- 0.27%, p = 0.048) and brainstem volume (- 0.16%, p = 0.021). CONCLUSIONS: This study supports previous observations regarding volume loss in several brain regions of patients with antiNMDAr encephalitis. Further analyses are required to understand the role of treatment and severe clinical forms, as well as the relationship between volume loss and functional outcome.

Acute kidney injury secondary to chlorine dioxide use for COVID-19 prevention.

Chlorine dioxide has been historically used as a disinfecting agent for drinking water supplies and surfaces. Widespread use as an alternative option for prevention and treatment of COVID-19 has emerged due to a lack of specific treatment. We present the case of a 55-year-old male who developed acute kidney injury and disseminated intravascular coagulation after chlorine dioxide prophylactic ingestion, with regression after therapy with hemodialysis.

Clinical experience of plasmapheresis for neuromyelitis optica patients in Mexico.

BACKGROUND: Neuromyelitis optica spectrum disorders (NMOSDs) are a group of chronic immune-mediated demyelinating diseases of the central nervous system. Their pathophysiology dependent on humoral mediated responses caused by autoreactive IgG antibodies against aquaporin-4 water channels (AQP4-IgG) or myelin oligodendrocyte glycoprotein (MOG-IgG). Plasma exchange (PLEX) has proved to be a beneficial therapy in patients with severe relapses. We present the largest series of Latin American patients treated with PLEX for acute NMOSDs relapses. METHODS: A retrospective study was conducted. Selection included patients diagnosed with NMOSDs who received PLEX between 2010-2019, irrespective of their AQP4-IgG serostatus. All patients received 5 grams of IV methylprednisolone. PLEX therapy could be initiated simultaneously or after IV steroids. Baseline and post-PLEX therapy Expanded Disability Status Scale (EDSS) was measured to identify acute response to therapy. Comparison between responders and non-responders was also conducted. Subgroup analysis stratified response by serostatus, type of clinical relapse and time to PLEX. RESULTS: A total of 89 patients were included. Mean age at onset was 38 ± 12.97 years. 49 (55.1%) patients were AQP4-IgG seropositive. Most patients had unilateral optic neuritis (34.8%) or longitudinally extensive transverse myelitis (33.7%). Mean time from onset to PLEX initiation was 20.9 ± 18.1 days. Response rate was 39.3% and mean decline in EDSS was 0.7 ± 0.9 (p <0.001). Decline in EDSS and response rate were independent of serostatus, type of clinical relapse or time to PLEX initiation. CONCLUSION: PLEX appears to be an effective therapy for NMOSDs relapses even in limited resources setting where treatment initiation may be delayed. The benefit seems to be independent of the type of clinical relapse and AQP4 IgG serostatus.

Socioeconomic status and access to multiple sclerosis treatment in Mexico.

INTRODUCTION: Multiple sclerosis (MS) is a chronic neurological autoimmune condition and the leading non-traumatic cause of neurological disability worldwide. Disease-modifying therapies (DMT) directly impact on the long-term prognosis of patients with MS preventing relapses and the associated disability progression. Here, we analyzed the impact of socioeconomic status (SES) on DMT access in Mexican patients. METHODS: We evaluated the association between SES and DMT access using the MS registry from the National Institute of Neurology and Neurosurgery in Mexico City. We included 974 patients with MS (McDonald 2010 criteria). We categorized SES according to the 2018 Mexican Association of Market Research Agencies (AMAI) SES classification. We analyzed DMT type, MS phenotype, educational level, symptomatic onset to diagnosis, EDSS at arrival, as well as the progression index. Chi-squared and Wilcoxon tests were used, and multivariable analysis performed for DMT access. RESULTS: When comparing the lower versus higher levels of SES, a significant association was found on the percentage of patients with higher levels of disability (EDSS >6) at arrival, the proportion of patients not receiving any DMT and a higher proportion of secondary progressive MS (p=0.006, p<0.001and p=0.004, respectively). We also found that lower educational levels had a significance and inverse association with EDSS on first visit (p=0.019), symptomatic onset to diagnosis (p<0.001) and a higher disability status at arrival (EDSS >6, p=0.010). CONCLUSIONS: Our study suggests that SES is an important factor determining not only prompt but overall access to highly effective DMT. Lower SES are associated with greater levels of disability at the first clinic visit and a higher proportion of patients not receiving DMT up to 12 months of follow-up.

Cyclophosphamide treatment in active multiple sclerosis.

OBJECTIVE: Cyclophosphamide (CYC) is an alkylating agent with immunosuppressive effect by inhibiting DNA synthesis and producing apoptosis used in many autoimmune diseases, including multiple sclerosis (MS). Here, we analyze the efficacy of CYC treatment in relapsing-remitting (RRMS) and active secondary progressive MS (SPMS) in our center with a monthly scheme. METHODS: Patients with MS treated with CYC and a follow up of at least 36 months were eligible for inclusion. All participants had received a standard CYC regimen. The EDSS score mean annualized relapse rate (ARR) and progression index (PI) were measured as efficacy outcomes at 12, 24, and 36 months. Outcomes were also analyzed comparing disease course and activity. RESULTS: A total of 16 patients were included (50% male, 18.75% RRMS and 81.25% SPMS). EDSS remained stable along the follow-up period, with 62.5% improving or maintaining the same EDSS score at 12 months. PI decreased 14% and 21% at 12 and 24-36 months of follow-up, respectively. ARR decreased 20% after 12 months, 19% after 24 months, and 30.23% after 36 months. Median differences in ARR were higher in patients with high relapse activity (0.60 vs 0.07, p = 0.001) and malignant course (0.60 vs 0.17, p = 0.027). PI also differed with higher mean differences in patients with high relapse activity (0.70 vs 0.03, p = 0.016) and malignant course (1.17 vs 0.03, p = 0.003). CONCLUSIONS: CYC continues to be a valid therapeutic option, especially in regions with limited access to high-efficiency therapies particularly in patients with high relapsing activity and malignant course.

Rituximab efficacy at different initial and maintenance doses in neuromyelitis optica spectrum disorder: Experience from a national health institute in México.

BACKGROUND: NMOSD is an inflammatory disorder of the central nervous system that primarily affects the optic nerves and spinal cord. Rituximab (RTX) is a monoclonal antibody directed against CD20, an epitope expressed on pre-B and mature B cells. It has of wide use in several antibody-mediated autoimmune diseases. OBJECTIVES: To demonstrate RTX clinical efficacy at different initial and maintenance doses administered in patients with NMOSD. METHODS: In this retrospective/observational study we recruited subjects with NMOSD with at least one RTX infusion. Annual relapse rates (ARR) were compared in several induction and maintenance regimens with RTX in 66 patients with NMOSD. RESULTS: Fifty-four (81.8%) were female and two thirds (66.7%) had positive anti-AQP4 antibodies. The most prevalent induction and maintenance regimens were 1000 mg on days 1 and 15 (51.5%) and 1000 mg every 6 months (40.9%), respectively. Overall, the annual relapse rate (ARR) decreased from 1.15 to 0.46 with RTX (p < 0.001). In patients with persistent relapses, the ARR decreased from 1.66 to 1.22, representing a relative risk reduction of 24%. Treatment with RTX decreased the ARR from 1.36 to 0.4 in the 500 mg induction and maintenance dose subgroup, and from 0.7 to 0.4 in the 1000 mg induction and maintenance dose subgroup. CONCLUSION: RTX treatment in patients with NMOSD demonstrated a marked and sustained reduction in the ARR, regardless of induction and maintenance regimens. EDSS stability was observed, even in patients with active and severe NMOSD.

Rituximab as an effective therapeutic option in refractory Neuro-Behçet syndrome.

INTRODUCTION: Behçet's disease (BD) is an inflammatory disease of unknown etiology with periods of relapses and remissions. Neuro-Behçet syndrome (NBS) is one of the main causes of long-term morbidity and mortality, making its prompt recognition and early treatment fundamental to achieving a better outcome. Currently there are no treatment guidelines either for BS or NB, making the management of these patients particularly difficult. CASE PRESENTATION: We present the case report of a patient with pseudo-tumoral lesion and myelitis refractory to steroids and cyclophosphamide who successfully showed remission after treatment with an anti-CD20 therapy. CONCLUSION: This is the first report of concomitant pseudo-tumoral lesion and myelitis secondary to BS. We found rituximab treatment to be a safe and effective therapeutic option for NB supported by the radiological and clinical improvement achieved in our patient.

Effect of rituximab on disease activity in latin American patients with anti-aquaporin-4 (+) neuromyelitis optica spectrum disorder.

OBJECTIVES: The aim of the present study is to explore the efficacy of rituximab in patients with Neuromyelitis Optica spectrum disorders (NMOsd) with positive AQP4-IgG serostatus. PATIENTS AND METHODS: In this single center retrospective study, we recruited seropositive anti-AQP4 NMOsd patients who received treatment with Rituximab (RTX) for at least 2 years. Demographics were described and annualized relapse rate (AAR) and survival analysis were performed for time to relapse with Rituximab. All p values ≤0.05 we considered statistically significant. RESULTS: A total of 15 patients (100 % female) were identified. Mean age of disease onset was 34 ±â€¯11 years, mean time of disease was 8.11 ±â€¯4.04 years and the median number of relapses was 5 (2-16). Ten patients received an immunosuppressive agent before RTX. Mean age of RTX initiation was 37 ±â€¯12 with a mean treatment duration of 52 ±â€¯28 months. The median ARR before and after treatment with RTX was 2.08 vs 0.00, respectively, with a difference of -2.08 (p < 0.001) CONCLUSIONS: This study shows a statistically significant reduction in the ARR and an increase in the relapse-free rate in AQP4-IgG NMOsd patients treated with RTX. These findings support the use of rituximab in our population, and indirectly suggests that its prompt use could modify the course of the disease.