Examining the Features of Neuroleptic Malignant Syndrome in Anti-NMDA Receptor Encephalitis: A Case-Control Study.

BACKGROUND: Anti-N-methyl-D-aspartate receptor encephalitis (ANMDARE) is a neuroimmunological disorder that frequently improves with immunotherapy. Symptomatic treatment with antipsychotics is common in the early stages when psychiatric symptoms predominate, and their use has been associated with serious side effects including neuroleptic malignant syndrome (NMS). The observation of an adverse response to antipsychotics, raising the suspicion of NMS, has been included as a criterion for possible autoimmune psychosis. METHODS: This case-control study included patients who received antipsychotics before referral to the National Institute of Neurology and Neurosurgery of Mexico, where they were diagnosed as having definite ANMDARE, and patients with ANMDARE who did not receive antipsychotics before referral. The neurologic and systemic features that are used to measure an adverse response to antipsychotics, raising the suspicion of NMS, were measured in both groups, including akinesia, autonomic instability, generalized rigidity, elevated concentrations of creatine phosphokinase, and hyperthermia. A logistic regression analysis was used to determine the relationship between the previous use of antipsychotics and the occurrence of NMS-like reactions. RESULTS: A total sample of 112 patients with definite ANMDARE were included in the study. Fifty patients received antipsychotics before being referred to our institution. In this group, thirty-six patients (72%) were initially classified as having an adverse response, raising the suspicion of NMS, with the following features: akinesia (64%), autonomic instability (58%), generalized rigidity (52%), elevated concentrations of creatine phosphokinase (50%), and hyperthermia (14%). Six patients fulfilled the criteria for NMS (12%). The comparison with patients who did not receive antipsychotics before the clinical assessment did not show a significant difference between groups regarding the frequency of akinesia, autonomic instability, generalized rigidity, elevated concentrations of creatine phosphokinase, or hyperthermia. Among different antipsychotics, only haloperidol was significantly associated with generalized rigidity as compared to patients who did not receive antipsychotics. CONCLUSIONS: Our study supports previous observations about the high frequency of autonomic dysfunction, hyperthermia, tachycardia, rigidity, and elevated creatine phosphokinase levels in patients with anti-NMDAR encephalitis following the administration of antipsychotic medications. Nevertheless, our study does not suggest a causal link between atypical antipsychotics and the onset of these neurological symptoms, as they were equally frequent among the group of patients who did not receive antipsychotic treatment.

Conversion Predictors of Clinically Isolated Syndrome to Multiple Sclerosis in Mexican Patients: A Prospective Study.

BACKGROUND: Clinically Isolated Syndrome (CIS) is the first clinical episode suggestive of Clinical Definite Multiple Sclerosis (CDMS). There are no reports on possible predictors of conversion to CDMS in Mexican mestizo patients. AIM OF THE STUDY: To investigate immunological markers, clinical and paraclinical findings, and the presence of herpesvirus DNA to predict the transition from CIS to CDMS in Mexican patients. METHODS: A single-center prospective cohort study was conducted with newly diagnosed patients with CIS in Mexico between 2006 and 2010. Clinical information, immunophenotype, serum cytokines, anti-myelin protein immunoglobulins, and herpes viral DNA were determined at the time of diagnosis. RESULTS: 273 patients diagnosed with CIS met the enrolment criteria; after 10 years of follow-up, 46% met the 2010 McDonald criteria for CDMS. Baseline parameters associated with conversion to CDMS were motor symptoms, multifocal syndromes, and alterations of somatosensory evoked potentials. The presence of at least one lesion on magnetic resonance imaging was the main factor associated with an increased risk of conversion to CDMS (RR 15.52, 95% CI 3.96-60.79, p = 0.000). Patients who converted to CDMS showed a significantly lower percentage of circulating regulatory T cells, cytotoxic T cells, and B cells, and the conversion to CDMS was associated with the presence of varicella-zoster virus and herpes simplex virus 1 DNA in cerebrospinal fluid and blood. CONCLUSION: There is scarce evidence in Mexico regarding the demographic and clinical aspects of CIS and CDMS. This study shows several predictors of conversion to CDMS to be considered in Mexican patients with CIS.

SARS-CoV-2 awakens ancient retroviral genes and the expression of proinflammatory HERV-W envelope protein in COVID-19 patients.

Patients with COVID-19 may develop abnormal inflammatory response, followed in some cases by severe disease and long-lasting syndromes. We show here that in vitro exposure to SARS-CoV-2 activates the expression of the human endogenous retrovirus (HERV) HERV-W proinflammatory envelope protein (ENV) in peripheral blood mononuclear cells from a subset of healthy donors, in ACE2 receptor and infection-independent manner. Plasma and/or sera of 221 COVID-19 patients from different cohorts, infected with successive SARS-CoV-2 variants including the Omicron, had detectable HERV-W ENV, which correlated with ENV expression in T lymphocytes and peaked with the disease severity. HERV-W ENV was also found in postmortem tissues of lungs, heart, gastrointestinal tract, brain olfactory bulb, and nasal mucosa from COVID-19 patients. Altogether, these results demonstrate that SARS-CoV-2 could induce HERV-W envelope protein expression and suggest its involvement in the immunopathogenesis of certain COVID-19-associated syndromes and thereby its relevance in the development of personalized treatment of patients.

Clinical outcomes and prognostic factors in patients with optic neuritis related to NMOSD and MOGAD in distinct ethnic groups from Latin America.

BACKGROUND: Optic neuritis (ON) can be an initial manifestation of neuromyelitis optica spectrum disorder (NMOSD) associated with aquaporin 4-antibody (AQP4-Ab) or myelin oligodendrocyte glycoprotein antibody (MOG-Ab)-associated disease (MOGAD). Additionally, both diseases may have overlapping paraclinical and radiological features. These diseases may have different outcomes and prognoses. We aimed to compare clinical outcomes and prognostic features of patients with NMOSD and MOGAD presenting ON as first attack, from different ethnic groups in Latin America. METHODS: We conducted a retrospective observational multicenter study in patients from Argentina (n = 61), Chile (n = 18), Ecuador (n = 27), Brazil (n = 30), Venezuela (n = 10) and Mexico (n = 49) with MOGAD or NMOSD related ON. Predictors of disability outcomes at last follow-up, namely visual disability (Visual Functional System Score ≥4), motor disability (permanent inability to walk further than 100 m unaided) and wheelchair dependence based on EDSS score were evaluated. RESULTS: After a mean disease duration of 42.7 (±40.2) months in NMOSD and 19.7 (±23.6) in MOGAD, 55% and 22% (p>0.001) experienced permanent severe visual disability (visual acuity from 20/100 to 20/200), 22% and 6% (p = 0.01) permanent motor disability and 11% and 0% (p = 0.04) had become wheelchair dependent, respectively. Older age at disease onset was a predictor of severe visual disability (OR=1,03 CI95%1.01-1.05, p = 0.03); older age at disease onset (OR=1,04 CI95%1.01-1.07, p = 0.01), higher number of relapses (OR=1,32 CI95%1.02-1.71, p = 0.03) and rituximab treatment (OR=0,36 CI95%0.14-0.90, p = 0.02) were predictors of permanent motor disability, whereas ON associated with myelitis at disease onset was a predictor of wheelchair dependency (OR=4,16, CI95%1.23-14.08, p = 0,02) in NMOSD patients. No differences were found when evaluating distinct ethnic groups (Mixed vs. Caucasian vs. Afro-descendant) CONCLUSIONS: NMOSD was associated with poorer clinical outcomes than MOGAD. Ethnicity was not associated with prognostic factors. Distinct predictors of permanent visual and motor disability and wheelchair dependency in NMOSD patients were found.

Therapeutic strategies in NMOSD and MOGAD patients: A multicenter cohort study in Latin America.

PURPOSE: This study describes the therapeutic strategies in NMOSD and MOGAD adopted by neurologists to treat both conditions in Latin America (LATAM) with main focus on rituximab (RTX) and the disease outcome. METHODS: retrospective study in a cohort of NMOSD and MOGAD patients followed in specialized MS/NMOSD centers from eight countries and 14 LATAM reference centers. Demographics and clinical characteristics were collected. RTX strategies on naïve (for rituximab) patients were summarized as follows: scheme A: two 1000 mg infusions 15 days apart and repeated every 6 months; scheme B: four 375 mg/m2 infusions every week for 4 weeks and repeated every 6 months; scheme C: one 1000 mg infusions and repeated every 6 months; scheme D: other scheme used. Relapse rate and adverse events during follow-up were analyzed considering the different RTX schemes. Poisson and logistic regression analysis were used to assess baseline aspects and disease activity during follow-up. RESULTS: A total of 217 patients were included. 197 were NMOSD patients (164, 83.2% AQP4-IgG seropositive and 16.7% seronegative) and 20 were MOGAD patients. The most frequent long-term treatment was RTX in both groups (48.2% and 65% for NMOSD and MOGAD patients, respectively). The most common RTX regimen used in 79 (83.1%) patients was two 1000 mg infusions 15 days apart and repeat every 6 months. Relapses under RTX treatment were observed in 21 (22.1%) patients. Relapses after RTX treatment were associated with higher EDSS (OR 1.75, 95%CI 1.44-2.34, p = 0.03) and higher ARR pre-RTX (OR = 2.17, 95% CI 1.72-3.12, p = 0.002) but not with RTX regimen (OR = 1.10, 95% CI 0.89-1.21, p = 0.60). CONCLUSION: the most strategy used in LATAM was RTX with two 1000 mg infusions 15 days apart. Relapses during follow up were not associated with RTX regimen used.

Quality of life and mental health in multiple sclerosis patients during the COVID-19 Pandemic.

BACKGROUND: The COVID-19 pandemic had a profound impact on mental health symptoms and quality of life (QoL) in the general population due to necessary public health restrictions such as social distancing. The psychosocial effect of the pandemic on vulnerable groups such as people living with Multiple Sclerosis (PwMS) has been scarcely explored in countries with additional socioeconomical burdens such as access to healthcare disparities METHODS: A questionnaire exploring sociodemographic variables, quality of life, mental health determinants and sleep quality was applied to 92 PwMS to explore changes prior and during the pandemic regarding these domains RESULTS: 58.8% of the subjects were female, median age was 37.1 (± 8.5) years and relapsing-remitting MS was the predominant clinical subtype (83.5%). Unemployment rate significantly increased during the pandemic (12.3% vs 27.8%; p= 0.001). Only 46.4% received medical follow-up care during the pandemic. QoL was affected predominantly due to limitations in instrumented activities of daily life (IADL). Neuropsychiatric symptoms, requiring healthcare during the pandemic, anxiety prior to the pandemic and restricted IADL were predictors of MS-related physical impact worsening, while decreased physical/emotional wellbeing selfcare, neuropsychiatric symptoms, bad sleep quality, anxiety prior to the pandemic and restricted non-instrumental ADL predicted aggravation of MS-related psychological impact measured by the MSIS-29. Curiously, specific items regarding anxiety were more prevalent prior to the pandemic (anxious mood; p=0.02, helplessness; p=0.01), sleep problems; p=0.001 and cardiovascular symptoms; p=0.001, nevertheless, stability was observed for most items. Importantly, 77.3% of PwMS reported at least one neuropsychiatric symptom CONCLUSION: The deleterious effects of the COVID-19 pandemic on psychosocial wellbeing in PwMS, QoL and mental health outcomes are frequently overseen in vulnerable populations such as PwMS. Albeit the limitations of this study, our results may help implement policies that prevent negative outcomes on psychosocial wellbeing due to public health measures (e.g., social distancing) in MS and other neurological diseases that inexorably need constant follow-up.

Diagnosis and classification of optic neuritis.

There is no consensus regarding the classification of optic neuritis, and precise diagnostic criteria are not available. This reality means that the diagnosis of disorders that have optic neuritis as the first manifestation can be challenging. Accurate diagnosis of optic neuritis at presentation can facilitate the timely treatment of individuals with multiple sclerosis, neuromyelitis optica spectrum disorder, or myelin oligodendrocyte glycoprotein antibody-associated disease. Epidemiological data show that, cumulatively, optic neuritis is most frequently caused by many conditions other than multiple sclerosis. Worldwide, the cause and management of optic neuritis varies with geographical location, treatment availability, and ethnic background. We have developed diagnostic criteria for optic neuritis and a classification of optic neuritis subgroups. Our diagnostic criteria are based on clinical features that permit a diagnosis of possible optic neuritis; further paraclinical tests, utilising brain, orbital, and retinal imaging, together with antibody and other protein biomarker data, can lead to a diagnosis of definite optic neuritis. Paraclinical tests can also be applied retrospectively on stored samples and historical brain or retinal scans, which will be useful for future validation studies. Our criteria have the potential to reduce the risk of misdiagnosis, provide information on optic neuritis disease course that can guide future treatment trial design, and enable physicians to judge the likelihood of a need for long-term pharmacological management, which might differ according to optic neuritis subgroups.

Onychomycosis Caused by Kloeckera apiculata: A Case Report in a Patient with Multiple Sclerosis.

We report the first case of onychomycosis caused by Kloeckera apiculata in a woman with multiple sclerosis. Video-dermoscopic examination showed a spiked pattern and distal irregular aspect. Colonies on Sabouraud agar were white, creamy, and smooth. A microscopic examination showed blastoconidia. MALDI-TOF confirmed Kloeckera apiculata as the causal agent.

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.

Clinical Significance of Delirium With Catatonic Signs in Patients With Neurological Disorders.

OBJECTIVE: According to DSM-5, catatonia and delirium are mutually exclusive clinical syndromes. The investigators explored the co-occurrence of delirium and catatonia (i.e., catatonic delirium) and the clinical significance of this syndrome with a sample of neurological patients. METHODS: This prospective study with consecutive sampling included patients diagnosed with delirium at the National Institute of Neurology and Neurosurgery of Mexico. DSM-5 criteria for delirium, the Confusion Assessment Method, and the Delirium Rating Scale-Revised-98 were used to select and characterize patients. Catatonia was assessed using the Bush-Francis Catatonia Rating Scale and DSM-5 diagnostic criteria. Logistic regression analysis was performed to identify etiological factors associated with catatonic delirium. RESULTS: A total of 264 patients with delirium were included, 61 (23%) of whom fulfilled the criteria for catatonia and delirium simultaneously. Brain tumors, subarachnoid hemorrhage, acute hydrocephalus, and ischemic stroke were associated with delirium without catatonic signs. Catatonic delirium was observed among patients with encephalitis, epilepsy, brain neoplasms, and brain tuberculosis. After multivariate analysis, the association between catatonic delirium and encephalitis (both viral and anti-N-methyl-d-aspartate receptor [NMDAR]) was confirmed. CONCLUSIONS: Delirium is a common complication of neurological diseases, and it can coexist with catatonia. The recognition of catatonic delirium has clinical significance in terms of etiology, as it was significantly associated with viral and anti-NMDAR encephalitis.

Chiasmatic lesions on conventional magnetic resonance imaging during the first event of optic neuritis in patients with neuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein-associated disease in a Latin American cohort.

BACKGROUND AND PURPOSE: Optic neuritis (ON) is often the initial symptom of neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein-associated disease (MOGAD). We aimed to compare the frequency and pattern of chiasmatic lesions in MOGAD-related ON (MOGAD-ON) and NMOSD-related ON (NMOSD-ON) using conventional brain imaging (magnetic resonance imaging [MRI]) in Latin America (LATAM). METHODS: We reviewed the medical records and brain MRI (≤30 days from ON onset) of patients with a first event of MOGAD-ON and NMOSD-ON. Patients from Argentina (n = 72), Chile (n = 21), Ecuador (n = 31), Brazil (n = 30), Venezuela (n = 10) and Mexico (n = 82) were included. Antibody status was tested using a cell-based assay. Demographic, clinical, imaging and prognostic (as measured by the Visual Functional System Score [VFSS] of the Expanded Disability Status Scale) data were compared. RESULTS: A total of 246 patients (208 NMOSD and 38 MOGAD) were included. No differences were found in gender and ethnicity between the groups. We observed chiasmatic lesions in 66/208 (31.7%) NMOSD-ON and in 5/38 (13.1%) MOGAD-ON patients (p = 0.01). Of these patients with chiasmatic lesions, 54/66 (81.8%) and 4/5 had associated longitudinally extensive optic nerve lesions, 45/66 (68%) and 4/5 had bilateral lesions, and 31/66 (47%) and 4/5 showed gadolinium-enhancing chiasmatic lesions, respectively. A positive correlation was observed between VFSS and presence of bilateral (r = 0,28, p < 0.0001), chiasmatic (r = 0.27, p = 0.0001) and longitudinally extensive lesions (r = 0,25, p = 0.0009) in the NMOSD-ON group, but no correlations were observed in the MOGAD-ON group. CONCLUSIONS: Chiasmatic lesions were significantly more common in NMOSD than in MOGAD during an ON attack in this LATAM cohort. Further studies are needed to assess the generalizability of these results.

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.

Interaction of HLA Class II rs9272219 and TMPO rs17028450 (Arg690Cys) Variants Affects Neuromyelitis Optica Spectrum Disorder Susceptibility in an Admixed Mexican Population.

Neuromyelitis Optica Spectrum Disorder (NMOSD) is a demyelinating autoimmune disease of the central nervous system, more prevalent in individuals of non-European ancestry. Few studies have analyzed genetic risk factors in NMOSD, and HLA class II gene variation has been associated NMOSD risk in various populations including Mexicans. Thymopoietin (TMPO) has not been tested as a candidate gene for NMOSD or other autoimmune disease, however, experimental evidence suggests this gene may be involved in negative selection of autoreactive T cells and autoimmunity. We thus investigated whether the missense TMPO variant rs17028450 (Arg630Cys, frequent in Latin America) is associated with NMOSD, and whether this variant shows an interaction with HLA-class II rs9272219, previously associated with NMOSD risk. A total of 119 Mexican NMOSD patients, 1208 controls and 357 Native Mexican individuals were included. The HLA rs9272219 "T" risk allele frequency ranged from 21 to 68%, while the rs17028450 "T" minor allele frequency was as high as 18% in Native Mexican groups. Both rs9272219 and rs17028450 were significantly associated with NMOSD risk under additive models (OR = 2.48; p = 8 × 10-10 and OR = 1.59; p = 0.0075, respectively), and a significant interaction between both variants was identified with logistic regression models (p = 0.048). Individuals bearing both risk alleles had an estimated 3.9-fold increased risk of NMOSD. To our knowledge, this is the first study reporting an association of TMPO gene variation with an autoimmune disorder and the interaction of specific susceptibility gene variants, that may contribute to the genetic architecture of NMOSD in admixed Latin American populations.

Clinical practice patterns in multiple sclerosis management: Mexican consensus recommendations.

BACKGROUND: Multiple sclerosis affects more than 2 million people. Clinical decisions are performed under evidence-based medicine. The appearance of new disease-modifying therapies and changes in diagnostic criteria complicates the decision-making process in clinical practice. OBJECTIVES: To characterize the criteria for radiologically isolated syndrome (RIS), clinically isolated syndrome (CIS), and relapsing-remitting multiple sclerosis (RRMS) by Mexican neurologists in a real-world setting. METHODS: A two-round modified Delphi method (RAND/UCLA) was applied. RESULTS: In RIS, LP, spinal cord MRI and VEP should be included in diagnostic testing; DMT initiation is not necessary. A follow-up MRI within 3 months are recommended. In CIS, corticosteroid therapy should be initiated at first relapse; both simple and Gd-enhanced MRI is mandatory. LP, selective blood tests, and NMO-IgG/AQP4 antibodies should be performed as complementary. IFN beta or GA were the most suitable DMTs for treating high-risk CIS. Patients with RRMS should begin with DMT at diagnosis, include a follow-up MRI if a patient had 2 relapses within 6 months. GA and oral DMTs are the most eligible DMTs for mild RRMS. Monoclonal antibodies-based therapy is chosen when disability is present. Radiological criteria for switching DMT included >1 Gd+ lesion and >2 new T2 lesions. CONCLUSIONS: Although many coincidences, there are still many hollows in the medical attention of MS in Mexico. This consensus recommendation could be helpful to implement better evidence-based recommendations and guidelines in a real-world setting.

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.

Onychomycosis in patients with multiple sclerosis: prevalence, clinical description, mycological, and dermoscopic study in a Mexican population.

BACKGROUND: Multiple sclerosis (MS) is a chronic demyelinating disease related to HLA-DR8. Susceptibility to onychomycosis has been found in Mexican mestizos with HLA-DR8. The frequency of onychomycosis in this neurological disease is unknown. OBJECTIVES: To determine the frequency of onychomycosis and its clinical, mycological, and dermoscopic characteristics in patients with MS in comparison with the general population. METHODS: Observational, cross-sectional, case-control study in patients with MS from October 2017 to February 2018. Age, gender, MS type, and time of progression from diagnosis to date and baseline treatment were collected after signed informed consent. A neurological exploration and clinical examination of fingernails and toenails for onychomycosis was conducted. Mycological and dermoscopic studies of the infected nails were performed on patients with clinical diagnosis of onychomycosis. A healthy control group was taken for each case (1:1), paired by age and gender. RESULTS: The frequency of onychomycosis in patients with MS was higher than the healthy population (32% vs. 26%, P = 0.509). A higher frequency of non-dermatophyte fungi was found, although it was not statistically significant. The clinical manifestations and dermoscopic findings in patients with MS and onychomycosis were similar to those of the general population. CONCLUSION: The frequency of onychomycosis in patients with MS is slightly higher than that of the general population. A possible association of HLA-DR8 as a susceptibility factor for onychomycosis is proposed. The etiology of opportunistic fungi in MS patients with onychomycosis may be related to immunosuppressive treatment.

An Abnormally High Neutrophil-to-Lymphocyte Ratio Is Not an Independent Outcome Predictor in AQP4-IgG-Positive NMOSD.

Background: The neutrophil-to-lymphocyte ratio (NLR) has been investigated in many autoimmune conditions as a biomarker of inflammation and/or disease activity. The role of NLR in AQP4-IgG-positive neuromyelitis optica spectrum disorders (NMOSD) is far from clear. In this study, NLR was evaluated in patients with AQP4-IgG-positive NMOSD at disease onset and its prognostic impact was subsequently assessed. Methods: In this multicenter study, we retrospectively included all recent/newly diagnosed treatment-naïve patients with AQP4-IgG-positive NMOSD (n=90) from three different countries in Latin America (LATAM): Argentina, Ecuador, and Mexico. NLR was compared between AQP4-IgG-positive NMOSD and healthy controls (HC, n = 365). Demographic, clinical, paraclinical (including imaging), and prognostic data at 12 and 24 months were also evaluated. Multivariate regression analysis was used to describe and identify independent associations between the log-transformed NLR and clinical (relapses and EDSS) and imaging (new/enlarging and/or contrast-enhancing MRI lesions) outcomes. Results: NLR was higher in NMOSD patients during the first attack compared with HC (2.9 ± 1.6 vs 1.8 ± 0.6; p<0.0001). Regardless of immunosuppressant's initiation at disease onset, NLR remained higher in NMOSD patients at 12 (2.8 ± 1.3; p<0.0001) and 24 (3.1 ± 1.6; p<0.0001) months. No association was found at 12 and 24 months between the log-transformed NLR and the presence of relapses, new/enlarging and/or contrast-enhancing MRI lesions, and/or physical disability. Conclusions: In this cohort of LATAM patients with AQP4-IgG-positive NMOSD, NLR was abnormally high in attacks but also during follow-up. However, a high NLR was not an independent predictor of clinical or imaging outcomes in our models.

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.