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.

Adherence to self-administering interferon-ß1a using RebiSmart® device in Mexican patients with relapsing multiple sclerosis.

BACKGROUND: Adherence to disease-modifying therapies is determinant to attain maximal clinical benefit in multiple sclerosis (MS). RebiSmart® is an electronic auto-injector for subcutaneous delivery of interferon ß-1a (INF-ß1a) that monitors adherence by featuring a log of each drug administration for objective evaluation. The aim of this study was to assess long-term adherence to INF-ß1a by using the RebiSmart® device in Mexican patients with relapsing MS. METHODS: This is an observational multicenter study on patients with relapsing MS treated with INF-ß1a subcutaneously delivered by the RebiSmart® device. Adherence was computed as the number of injections received during the study period divided by the number of injections scheduled and expressed as percent. RESULTS: A total of 66 patients from 6 specialized MS centers were evaluated (45 females and 21 males, mean age 43.91±13.32 years). Mean adherence was 79.51±18% (median: 85.54%, range: 34.4-100%). During a median follow-up of 27.5 months (mean 33.36±29.39 months) the annualized relapse rate had a mean of 0.50±1.63. Mean initial EDSS was 1.90±1.52, and mean EDSS at the end of follow-up was 1.80±1.74. Compared with their counterparts, the mean number of relapses was significantly lower among patients with high (>80%) adherence (0.25±0.44 vs 0.67±92 relapses, respectively; P = 0.03). The proportion of relapse-free patients was 75.0% among patients with high adherence and 53.3% in low-compliant patients (P = 0.06). High adherence patients presented lower rates of EDSS worsening ≥1.0 at the end of treatment, as compared with low-compliant patients (11.1% vs 43.3%, respectively; P = 0.003). High schooling (>12 years) was the only predictor of a high adherence (OR: 2.97, 05% CI: 1.08-1.18; P = 0.03) and of being relapse-free during follow-up (OR: 3.22, 05% CI: 1.12-9.23; P = 0.03). CONCLUSION: Adherence to INF-ß1a using RebiSmart® in this Mexican cohort with MS was moderate, but associated with low relapse rate and influenced by high schooling.

Consenso para el diagnóstico y tratamiento de la esclerosis múltiple en pacientes del ISSSTE / Consensus for the diagnosis and treatment of multiple sclerosis in ISSSTE patients

Resumen: La esclerosis múltiple es una de las principales enfermedades desmielinizantes del sistema nervioso central, que repercute no solo en lo económico, sino también en lo social. El Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado (ISSSTE) dispone de la mayor parte de los tratamientos que modifican la evolución de esta enfermedad y para optimizar su uso, un grupo de neurólogos de la institución se reunió para la realización de un documento sobre aspectos generales de diagnóstico y tratamiento denominado Consenso para el Diagnóstico y Tratamiento de la Esclerosis múltiple en pacientes del ISSSTE. El objetivo de este documento es dar recomendaciones de las diferentes alternativas terapéuticas contra la esclerosis múltiple.

Abstract: Multiple sclerosis is one of the main demyelinating diseases of the central nervous system, which impacts not only economically but also socially. The Mexican Institute of Security and Social Services of State Workers (ISSSTE) has most of the disease modifying treatments for this disease and to optimize its use, a group of neurologists from the institution met to make a document on general aspects of diagnosis and treatment called: Consensus for the diagnosis and treatment of multiple sclerosis in ISSSTE patients. The objective of this consensus is to give recommendations on the different therapeutic alternatives against multiple scle- rosis for adults and children.

Central adiposity and mortality after first-ever acute ischemic stroke.

BACKGROUND: The waist-to-height ratio (WHtR) may be a better adiposity measure than the body mass index (BMI). We evaluated the prognostic performance of WHtR in patients with acute ischemic stroke (AIS). METHODS: First, we compared WHtR and BMI as adiposity measures in 712 healthy adults by tetrapolar bioimpedance analysis. Thereafter, baseline WHtR was analyzed as predictor of 12-month all-cause mortality in 821 Mexican mestizo adults with first-ever AIS by a Cox proportional hazards model adjusted for baseline predictors. RESULTS: In healthy individuals, WHtR correlated higher than BMI with total fat mass and showed a higher accuracy in identifying a high percentage of body fat (p < 0.01). In AIS patients a U-shaped relationship was observed between baseline WHtR and mortality (fatality rate 29.1%). On multivariate analysis, baseline WHtR ≤ 0.300 or >0.800 independently predicted 12-month all-cause mortality (hazard ratio 1.91, 95% confidence interval 1.04-3.51). BMI was not associated with mortality, tested either as continuous, binomial or stratified variable. CONCLUSION: WHtR is a modifiable risk factor that accurately demonstrates body fat excess. Extreme WHtR values were associated with increased 12-month all-cause mortality in Mexican mestizo patients with AIS. No survival advantage was found with high WHtR as the pragmatic indicator of obesity in this population.

Serum uric acid and outcome after acute ischemic stroke: PREMIER study.

BACKGROUND: Current evidence shows that uric acid is a potent antioxidant whose serum concentration increases rapidly after acute ischemic stroke (AIS). Nevertheless, the relationship between serum uric acid (SUA) levels and AIS outcome remains debatable. We aimed to describe the prognostic significance of SUA in AIS. METHODS: We studied 463 patients (52% men, mean age 68 years, 13% with glomerular filtration rate <60 ml/min at hospital arrival) with AIS pertaining to the multicenter registry PREMIER, who had SUA measurements at hospital presentation. Multivariate models were constructed to analyze the association of SUA with functional outcome as assessed by the modified Rankin scale (mRS) at 30-day, 3-, 6- and 12-month follow-up. A mRS 0-1 was regarded as a very good outcome. RESULTS: Mean SUA concentration at hospital arrival was 6.1 ± 3.7 mg/dl (362.8 ± 220.0 µmol/l). Compared with cases with higher SUA levels at hospital admission, patients with ≤4.5 mg/dl (≤267.7 µmol/l; the lowest tertile of the sample) had more cases of a very good 30-day outcome (30.5 vs. 18.9%, respectively; p = 0.004). SUA was not associated with mortality or functional dependence (mRS >2) at 30 days, or with any outcome measure at 3, 6 or 12 months poststroke. After adjustment for age, gender, stroke type and severity (NIHSS <9), time since event onset, serum creatinine, hypertension, diabetes and smoking, a SUA ≤4.5 mg/dl (≤267.7 µmol/l) was positively associated with a very good short-term outcome (odds ratio: 1.76, 95% confidence interval: 1.05-2.95; negative predictive value: 81.1%), but not at 3, 6 or 12 months of follow-up. When NIHSS was entered in the multivariate model as a continuous variable, the independent association of SUA with outcome was lost. Compared with cases with higher levels, patients with SUA ≤4.5 mg/dl (≤267.7 µmol/l) were more frequently younger than 55 years, women, with mild strokes, with normal serum creatinine and fewer had hypertension. The time since event onset to hospital arrival was not significantly associated with AIS severity or SUA levels; nevertheless, a nonsignificant tendency was observed for patients with severe strokes and high SUA levels arriving in <24 h. CONCLUSIONS: A low SUA concentration is modestly associated with a very good short-term outcome. Our findings support the hypothesis that SUA is more a marker of the magnitude of the cerebral infarction than an independent predictor of stroke outcome.

Cerebral venous thrombosis in a Mexican multicenter registry of acute cerebrovascular disease: the RENAMEVASC study.

BACKGROUND: Cerebral venous thrombosis (CVT) is a rare form of cerebrovascular disease that is usually not mentioned in multicenter registries on all-type acute stroke. We aimed to describe the experience on hospitalized patients with CVT in a Mexican multicenter registry on acute cerebrovascular disease. METHODS: CVT patients were selected from the RENAMEVASC registry, which was conducted between 2002 and 2004 in 25 Mexican hospitals. Risk factors, neuroimaging, and 30-day outcome as assessed by the modified Rankin scale (mRS) were analyzed. RESULTS: Among 2000 all-type acute stroke patients, 59 (3%; 95% CI, 2.3-3.8%) had CVT (50 women; female:male ratio, 5:1; median age, 31 years). Puerperium (42%), contraceptive use (18%), and pregnancy (12%) were the main risk factors in women. In 67% of men, CVT was registered as idiopathic, but thrombophilia assessment was suboptimal. Longitudinal superior sinus was the most frequent thrombosis location (78%). Extensive (>5 cm) venous infarction occurred in 36% of patients. Only 81% of patients received anticoagulation since the acute phase, and 3% needed decompressive craniectomy. Mechanical ventilation (13.6%), pneumonia (10.2%) and systemic thromboembolism (8.5%) were the main in-hospital complications. The 30-day case fatality rate was 3% (2 patients; 95% CI, 0.23-12.2%). In a Cox proportional hazards model, only age <40 years was associated with a mRS score of 0 to 2 (functional independence; rate ratio, 3.46; 95% CI, 1.34-8.92). CONCLUSIONS: The relative frequency of CVT and the associated in-hospital complications were higher than in other registries. Thrombophilia assessment and acute treatment was suboptimal. Young age is the main determinant of a good short-term outcome.

Spontaneous intracerebral hemorrhage in Mexico: results from a Multicenter Nationwide Hospital-based Registry on Cerebrovascular Disease (RENAMEVASC).

INTRODUCTION: Scarce information exists on intracerebral hemorrhage (ICH) in Latin America, and the existent is derived from single-center registries with non-generalizable conclusions. The aim of this study is to describe the frequency, etiology, management and outcome of ICH in Mexico. PATIENTS AND METHODS: We studied consecutive patients with ICH pertaining to the National Multicenter Registry on Cerebro-vascular Disease (RENAMEVASC), conducted in 25 centers from 14 states of Mexico. The Intracerebral Hemorrhage Grading Scale (ICH-GS) at admission was used to assess prognosis at 30 days follow-up. RESULTS: Of 2,000 patients with acute cerebrovascular disease registered in RENAMEVASC, 564 (28%) had primary ICH (53% women; median age: 63 years; interquartile range: 50-75 years). Hypertension (70%), vascular malformations (7%) and amyloid angiopathy (4%) were the main etiologies. In 10% of cases etiology could not be determined. Main ICH locations were basal ganglia (50%), lobar (35%) and cerebellum (5%). Irruption into the ventricular system occurred in 43%. Median score of ICH-GS was 8 points: 49% had 5-7 points, 37% had 8-10 points and 15% had 11-13 points. The 30-day case fatality rate was 30%, and 31% presented severe disability. The 30-day survival was 92% for patients with ICH-GS 5-7 points, whereas it decreased to 27% in patients with ICH-GS 11-13 points. CONCLUSIONS: In Mexico, ICH represents about a third of the forms of acute cerebrovascular disease, and the majority of patients present severe disability or death at 30 days of follow-up. Hypertension is the main cause; hence, control of this important cardiovascular risk factor should reduce the health burden of ICH.

[Obesity paradox and functional recovery in first-ever acute ischemic stroke survivors: the PREMIER study]. / Paradoja de la obesidad y recuperación funcional en sobrevivientes a un primer infarto cerebral: estudio PREMIER.

INTRODUCTION: The 'obesity paradox' is the decreasing risk of death after cardiovascular disease, with a high body mass index (BMI), even when BMI is a risk factor for vasculopathy, in the first place. Our aim was to analyze the influence of obesity on the functional recovery after ischemic stroke. PATIENTS AND METHODS: We studied 510 patients who survived a first-ever acute ischemic stroke, without cerebrovascular disease history, and without recurrence or death after 12 months of follow-up. We also studied 501 healthy subjects who received tetrapolar bioimpedance analysis to compare the waist-to-height ratio (WHtR), abdominal circumference and BMI, as adiposity indices, in order to apply them in stroke patients. RESULTS: In healthy individuals, WHtR performed better than BMI or abdominal circumference in predicting body fat. In a Cox proportional hazards model adjusted for multiple covariables, age (hazard ratio, HR = 1.11; 95% confidence interval, 95% CI = 1.08-1.14), NIHSS score (HR = 1.03; 95% CI = 1.01-1.05) and WHtR > 70 (HR = 2.44; 95% CI = 1.33-4.48) were associated with a high risk of attaining a modified Rankin scale more or equal than 3 at 12 months after stroke; whereas BMI > 35 (HR = 0.33; 95% CI = 0.11-0.98) was protector. CONCLUSION: As reflected by WHtR, the excess of adiposity increases the chance of severe disability after ischemic stroke. Since BMI reflects also total lean mass, it is risky to conclude that there is a protective effect of obesity alone in the functional recovery after stroke; nevertheless, it is possible that a certain magnitude of body mass is necessary to prevent severe disability in stroke survivors.

Acute care and one-year outcome of Mexican patients with first-ever acute ischemic stroke: the PREMIER study.

INTRODUCTION: Information on acute care and outcome of Mexican patients with ischaemic stroke is lacking. The aim of this report is to provide results of a first step stroke surveillance system and outcome at one year of follow-up. PATIENTS AND METHODS: In the PREMIER study 1,376 patients from 59 Mexican hospitals were included from January 2005 to June 2006. Of these, 1,040 (52% women, mean age 67.5 years) with first-ever cerebral infarction are here analyzed. Five visits were completed during the one year follow-up. RESULTS: Main risk factors were hypertension (64%), obesity (51%) and diabetes (35%). Total anterior circulation stroke syndrome occurred in 19% of patients, partial anterior in 38%, lacunar in 26% and posterior stroke syndrome in 17% cases. In 8% the stroke mechanism was large-artery atherosclerosis, in 18% cardioembolism, in 20% lacunar, in 6% miscellaneous mechanisms and in 42% the mechanism was undetermined, mainly due to a low use of diagnostic resources. Although 17% of patients arrived in < 3 h from stroke onset, only 0.5% had IV thrombolysis. Only 1% received endarterectomy or stenting. The 30-day case fatality rate was 15%. At one-year of follow-up, 47% had a modified Rankin score 0-2 (independent), 23% had 2-5 (dependent) and 29% died. One-year acute ischaemic stroke recurrence rate was 8%. CONCLUSION: In Mexico a significant proportion of patients arrive on time for thrombolysis, but very few receive this therapy. There is a low use of diagnostic resources to assign aetiology. Thirty-day case fatality rate doubles at 1-year after acute ischaemic stroke.

Aneurysmal subarachnoid hemorrhage in a Mexican multicenter registry of cerebrovascular disease: the RENAMEVASC study.

BACKGROUND: Information on risk factors and outcome of persons with aneurysmal subarachnoid hemorrhage (SAH) in Mexico is unknown. We sought to describe the clinical characteristics, risk factors, and outcome at discharge of Mexican patients with aneurysmal SAH. METHODS: A first-step surveillance system was conducted on consecutive cases confirmed by 4-vessel angiography from November 2002 to October 2004 in 25 tertiary referral centers. Age- and sex-matched control subjects were randomly selected by a 1:1 factor, for multivariate analysis on risk factors. RESULTS: We studied 231 patients (66% women; mean age 52 years, range 16-90 years). In 92%, the aneurysms were in the anterior circulation, and 15% had more than two aneurysms. After multivariate analysis, hypertension (odds ratio 2.46, 95% confidence interval 1.59-3.81) and diabetes mellitus (odds ratio 0.34, 95% confidence interval 0.17-0.68) were directly and inversely associated with aneurysmal SAH, respectively. Median hospital stay was 23 days (range 2-98 days). Invasive treatment was performed in 159 (69%) patients: aneurysm clipping in 126 (79%), endovascular coiling in 29 (18%), and aneurysm wrapping in 4 (2%). The in-hospital mortality was 20% (mostly due to neurologic causes), and 25% of patients were discharged with a modified Rankin score of 4 or 5. CONCLUSIONS: Hypertension is the main risk factor for aneurysmal SAH in hospitalized patients from Mexico. The female:male ratio is 2:1. A relatively low in-hospital mortality and a high frequency of invasive interventions are observed. However, a high proportion of patients are discharged with important neurologic impairment.