Epidemiology of NMOSD in Catalonia: Influence of the new 2015 criteria in incidence and prevalence estimates.

BACKGROUND: Population-based studies on neuromyelitis optica spectrum disorders (NMOSD) are limited, and it is unclear whether the rates have changed with the implementation of the new 2015 criteria. OBJECTIVES: To estimate the incidence and prevalence of NMOSD in Catalonia (Spain), using both the 2006 and the 2015 criteria. METHODS: In this clinic-based retrospective study, patients diagnosed with NMOSD between 2006 and 2015 were identified using multiple sources, including direct contact to all Catalan hospitals, identification of cases through the Catalan Health Surveillance System, and registry of antibodies to aquaporin-4 (AQP4-IgG) and myelin oligodendrocyte glycoprotein (MOG-IgG) in a reference laboratory. The incidence rate was calculated for the period 1 January 2006-1 January 2016 and prevalence for the date 1 January 2016. RESULTS: We identified 74 patients (by the 2015 criteria). Most patients were Caucasian (81%), and female (76%) with a median age at disease onset of 42 years (range, 10-76 years). In total, 54 (73%) patients were positive for AQP4-IgG, 11 (15%) double-seronegative, and 9 (12%) MOG-IgG-positive. Rates of incidence and prevalence (0.63/1,000,000 person-years and 0.89/100,000, respectively) were 1.5-fold higher than those reported by the 2006 criteria. Lowest rates were seen in children and elder people and highest in women and middle-aged people (40-59 years). The female predominance was lost in incident AQP4-IgG-seronegative children and AQP4-IgG-positive elder people. MOG-IgG and double-seronegativity contributed similarly but did not influence the long-term outcome. CONCLUSION: The new criteria increase the estimates, but NMOSD remains as a rare disease. The differences in age- and sex-specific estimates highlight the importance of the serologic classification.

Direct and indirect costs of Multiple Sclerosis in Baix Llobregat (Catalonia, Spain), according to disability.

BACKGROUND: Multiple sclerosis (MS) is an incurable chronic disease that predominantly affects young adults. It has a high socio-economic impact which increases as disability progresses. An assessment of the real costs of MS may contribute to our knowledge of the disease and to treat it more efficiently. Our objective is to assess the direct and indirect costs of MS from a societal perspective, in patients monitored in our MS Unit (Baix Llobregat, Catalonia) and grouped according to their disability (EDSS). METHODS: We analysed data from 200 MS patients, who answered a questionnaire on resource consumption, employment and economical status. Mean age was 41.6 years, mean EDSS 2.7, 65.5% of patients were female, 79.5% had a relapsing-remitting course, and 67.5% of them were receiving immunomodulatory treatment (IT). Patients were grouped into five EDSS stages. Data from the questionnaires, hospital charts, Catalan Health Service tariffs, and figures from Catalan Institute of Statistics were used to calculate the direct and indirect costs. The cost-of-illness method, and the human capital approach for indirect costs, were applied. Sensitivity analyses were performed to strengthen results. RESULTS: The mean total annual cost of MS per patient results 24,272 euros. This cost varied according to EDSS: 14,327 euros (EDSS = 0), 18,837 euros (EDSS = 1-3), 27,870 euros (EDSS = 3.5-5.5), 41,198 euros (EDSS = 6-7) and 52,841 euros (EDSS>7.5). When the mean total annual costs was adjusted by the mean % of patients on IT in our Unit (31%) the result was 19589 euros. The key-drivers for direct costs were IT in low EDSS stages, and caregiver costs in high stages. Indirect costs were assessed in terms of the loss of productivity when patients stop working. Direct costs accounted for around 60% of total costs in all EDSS groups. IT accounts from 78% to 11% of direct costs, and decreased as disability progressed. CONCLUSION: The total mean social costs of MS in a cohort from Baix Llobregat (Catalonia) were estimated at 24,272 euros per patient/year, and ranged between 14,327 euros (EDSS = 0) and 52,841 euros (EDSS = 7.5-9.5). Total costs, and particularly informal and direct costs, increased as the disability progressed. IT should be able to delay the progression of disability to be efficient and not only effective.

Epistasis between HLA-DRB1 parental alleles in a Spanish cohort with multiple sclerosis.

BACKGROUND AND OBJECTIVE: Multiple sclerosis (MS) has been consistently associated with the HLA-DR2 haplotype and particularly with the HLA-DRB1*15 allele. Epistatic interactions between both parental alleles in the DRB1 loci have been shown to modify the MS susceptibility risk. This study investigated the frequencies of various HLA-DRB1 genotypes, their impact on MS susceptibility and their correlation with the clinical severity in a Spanish population. METHODS: A genotype was considered as the combination of the two parental DRB1 alleles. We compared the frequencies of the genotypes in a sporadic MS population (n=380) with those of an unrelated healthy control cohort (n=1088). We correlated the different genotypes with the age at onset, gender distribution, symptoms at onset, course of the disease and progression severity by means of the time to reach the progressive phase and EDSS scores of 3 and 6. RESULTS: We found 81 different genotypes. There were four different MS-predisposing genotypes. Three of them contained the DRB1*15 allele (DRB1*03/15, DRB1*04/15, and DRB1*08/15) and the fourth was homozygote for the DRB1*03 allele. The highest odds ratio was found with the genotype DRB1*08/15 (OR=3.88, 95% CI=1.83-8.26, p<0.01), followed by DRB1*03/03 (OR=3.15, 95% CI=1.93-5.14, p<0.01), DRB1*03/15 (OR=2.72, 95% CI=1.88-3.94, p<0.01) and DRB1*04/15 (OR=2.54, 95% CI=1.64-3.98, p<0.01). The DRB1*01/04 and the DRB1*15/15 genotypes were associated with a shorter time to reach an EDSS score of 6. CONCLUSIONS: Our results show the importance of epistatic interactions among the HLA-DRB1 alleles, modifying the risk for MS as well as its clinical severity.

Adult herpes simplex encephalitis: fifteen years' experience.

INTRODUCTION: Herpes simplex encephalitis (HSE) is the most frequent cause of sporadic necrotizing encephalitis in adults. The aim of this study is to describe the characteristics of HSE and the factors influencing its outcome. MATERIAL AND METHODS: Retrospective study of patients diagnosed with HSE in a tertiary care teaching hospital over a 15-year period. Diagnosis was based on a consistent clinical profile for HSE, plus either a PCR-positive CSF HSV study or consistent brain neuroimaging findings. Patients were divided into 2 groups according to the modified Rankin Scale: good outcome (Grades <=2) and poor outcome (Grades >=3). RESULTS: Thirty-five patients were included. Mean age was 53.9 years. More than half presented febricula or fever, headache, disorientation, behavioral changes, decreased level of consciousness, or neurological deficit. CSF glucose concentration was normal in all patients and WBC count was normal in 8 (23%). PCR for HSV was positive in 92% and cranial MRI was suggestive of HSE in 100% of patients. Mortality was 8.6%. In relation to outcome, age (OR=1.079; 95% CI, 1.023-1.138) and serum albumin level at admission (OR=0.87; 95% CI, 0.794-0.954) were independent prognostic factors at discharge. At 6 months, days of fever after initiation of acyclovir therapy (OR=1.219; 95% CI, 1.046-1.422) and serum albumin level at admission (OR=0.917; 95% CI, 0.87-0.967) were independent prognostic factors. CONCLUSIONS: Normal brain MRI or detection of low CSF glucose concentration requires consideration of diagnoses other than HSE. Age, serum albumin level at admission, and days of fever after initiation of acyclovir therapy were independent prognostic factors of the disease.

Encefalitis herpética del adulto: experiencia de 15 años / Adult herpes simplex encephalitis: Fifteen years’ experience

Introduction: Herpes simplex encephalitis (HSE) is the most frequent cause of sporadic necrotizing encephalitis in adults. The aim of this study is to describe the characteristics of HSE and the factors influencing its outcome. Material and methods: Retrospective study of patients diagnosed with HSE in a tertiary care teaching hospital over a 15-year period. Diagnosis was based on a consistent clinical profile for HSE, plus either a PCR-positive CSF HSV study or consistent brain neuroimaging findings. Patients were divided into 2 groups according to the modified Rankin Scale: good outcome (Grades ≤2) and poor outcome (Grades ≥3).Results: Thirty-five patients were included. Mean age was 53.9 years. More than half presented febricula or fever, headache, disorientation, behavioral changes, decreased level of consciousness, or neurological deficit. CSF glucose concentration was normal in all patients and WBC count was normal in 8 (23%). PCR for HSV was positive in 92% and cranial MRI was suggestive of HSE in 100% of patients. Mortality was 8.6%. In relation to outcome, age (OR=1.079; 95% CI, 1.023–1.138) and serum albumin level at admission (OR=0.87; 95% CI, 0.794–0.954) were independent prognostic factors at discharge. At 6 months, days of fever after initiation of acyclovir therapy (OR=1.219; 95% CI, 1.046–1.422) and serum albumin level at admission (OR=0.917; 95% CI, 0.87–0.967) were independent prognostic factors.Conclusions: Normal brain MRI or detection of low CSF glucose concentration requires consideration of diagnoses other than HSE. Age, serum albumin level at admission, and days of fever after initiation of acyclovir therapy were independent prognostic factors of the disease (AU)

Introducción: la encefalitis herpética (EH) es la causa más frecuente de encefalitis necrosante esporádica del adulto. El objetivo es describir las características de la EH y sus factores pronósticos. Material y métodos: estudio retrospectivo de los pacientes ingresados en un hospital universitario de tercernivel y diagnosticados de EH durante un periodo de 15 años. El diagnóstico se estableció según el cuadro clínico compatible, junto con una prueba de reacción en cadena de la polimerasa(PCR) positiva para el virus del herpes simple (VHS) y/o una prueba de neuro imagen compatible. Se dividió a los pacientes en dos grupos de acuerdo con la Escala de Rankin modificada: buen pronóstico (grados p2) y mal pronóstico(grados X3).Resultados: se estudió a un total de 35 pacientes con una media de edad de 53,9 años. La mayoría presentaba febrícula o fiebre, cefalea, desorientación, alteración conductual, disminución del nivel deconciencia o focalidad neurológica. Todos los pacientes presentaron normoglucorraquia y el recuento leucocitario en el líquido cefalorraquídeo fue normal en 8 (23%)pacientes. La PCR para VHS resultó positiva en el 92% y la resonancia magnética (RM) craneal fue compatible con EH en el 100% de los pacientes. La mortalidad fue del 8,6%. La edad (odds ratio [OR] ¼ 1,079; intervalo de confianza [IC]del 95%, 1,023–1,138) y las concentraciones de seroalbúmina al ingreso (OR ¼ 0,87; IC del 95%, ,0,794–0,954) resultaron factores pronósticos independientes al alta. A los 6 meses, los días de fiebre después de la instauración del tratamiento con aciclovir (OR ¼ 1,219; ICdel95%, 1,046–1,422) y las concentraciones de seroalbúmina al ingreso (OR ¼ 0,917; IC del 95%, 0,87–0,967) resultaron factores pronósticos independientes (AU)