Prognostic factors associated with disability in a cohort of neuromyelitis optica spectrum disorder and MOG-associated disease from a nationwide Portuguese registry.

INTRODUCTION: Neuromyelitis optica spectrum disorders (NMOSD) and MOG-associated disease (MOGAD) are an increasingly recognized group of demyelinating disorders of the central nervous system. Previous studies suggest that prognosis is predicted by older age at onset, number of relapses, the severity of the first attack and autoantibody status. OBJECTIVE: To study prognostic factors associated with disability progression and additional relapses in the 3-year follow-up of a national NMOSD/MOGAD cohort. RESULTS: Out of 180 of the initial Portuguese cohort, data on 82 patients was available at the end of the follow-up period (2019-2022). Two patients died. Twenty (24.4%) patients had one or more attack in this period (25 attacks in total), mostly transverse myelitis (TM) (56.0%) or optic neuritis (32.0%). MOGAD was significantly associated with a monophasic disease course (p = 0.03), with milder attacks (p = 0.01), while AQP4 + NMOSD was associated with relapses (p = 0.03). The most common treatment modalities were azathioprine (38.8%) and rituximab (18.8%). AQP4 + NMOSD more frequently required chronic immunosuppressive treatment, particularly rituximab (p = 0.01). Eighteen (22.5%) had an EDSS ≥6 at the end of the follow-up. AQP4 + NMOSD (p < 0.01) and the occurrence of transverse myelitis (TM) during disease (p = 0.04) correlated with an EDSS≥6 at the end of the follow-up period. MOGAD was significantly associated with an EDSS<6 (p < 0.01), and MOG+ cases that reached an EDSS>6 were significantly older (64.0 ± 2.8 versus 31.0 ± 17.1, p = 0.017). A bivariate logistic regression model including the serostatus and TM attacks during disease history successfully predicted 72.2% of patients that progressed to an EDSS≥6. CONCLUSION: This study highlights that myelitis predict increased disability (EDSS≥6) in NMOSD/MOGAG and AQP4 positivity is associated with increased disability.

Late onset neuromyelitis optica spectrum disorders (LONMOSD) from a nationwide Portuguese study: Anti-AQP4 positive, anti-MOG positive and seronegative subgroups.

INTRODUCTION: Several neuroimmunological disorders have distinct phenotypes according to the age of onset, as in multiple sclerosis or myasthenia gravis. It is also described that late onset NMOSD (LONMOSD) has a different phenotype. OBJECTIVE: To describe the clinical/demographic characteristics of the LONMOSD and distinguish them from those with early onset (EONMOSD). METHODS: From a nationwide Portuguese NMOSD study we analyzed the clinical/demographic characteristics of the LONMOSD. RESULTS: From the 180 Portuguese patients 45 had disease onset after 50 years old, 80% were female. 23 had anti-AQP4 antibodies (51.1%), 13 anti-MOG antibodies (28.9%) and 9 were double seronegative (20.0%). The most common presenting phenotypes in LONMOSD were transverse myelitis (53.3%) and optic neuritis (26.7%), without difference from EONMOSD (p = 0.074). The mean EDSS for LONMOSD was 6.0 (SD=2.8), after a mean follow-up time of 4.58 (SD=4.47) years, which was significantly greater than the mean EDSS of EONMOSD (3.25, SD=1.80)(p = 0.022). Anti-AQP4 antibodies positive LONMOSD patients had increased disability compared to anti-MOG antibodies positive LONMOSD (p = 0.022). The survival analysis showed a reduced time to use a cane for LONMOSD, irrespective of serostatus (p<0.001). CONCLUSIONS: LONMOSD has increased disability and faster progression, despite no differences in the presenting clinical phenotype were seen in our cohort.

Neuromyelitis optica spectrum disorders: A nationwide Portuguese clinical epidemiological study.

INTRODUCTION: Neuromyelitis optica spectrum disorder (NMOSD) is a rare disorder in which astrocyte damage and/or demyelination often cause severe neurological deficits. OBJECTIVE: To identify Portuguese patients with NMOSD and assess their epidemiological/clinical characteristics. METHODS: This was a nationwide multicenter study. Twenty-four Portuguese adult and 3 neuropediatric centers following NMOSD patients were included. RESULTS: A total of 180 patients met the 2015 Wingerchuk NMOSD criteria, 77 were AQP4-antibody positive (Abs+), 67 MOG-Abs+, and 36 seronegative. Point prevalence on December 31, 2018 was 1.71/100,000 for NMOSD, 0.71/100,000 for AQP4-Abs+, 0.65/100,000 for MOG-Abs+, and 0.35/100,000 for seronegative NMOSD. A total of 44 new NMOSD cases were identified during the two-year study period (11 AQP4-Abs+, 27 MOG-Abs+, and 6 seronegative). The annual incidence rate in that period was 0.21/100,000 person-years for NMOSD, 0.05/100,000 for AQP4-Abs+, 0.13/100,000 for MOG-Abs+, and 0.03/100,000 for seronegative NMOSD. AQP4-Abs+ predominated in females and was associated with autoimmune disorders. Frequently presented with myelitis. Area postrema syndrome was exclusive of this subtype, and associated with higher morbidity/mortality than other forms of NMOSD. MOG-Ab+ more often presented with optic neuritis, required less immunosuppression, and had better outcome. CONCLUSION: Epidemiological/clinical NMOSD profiles in the Portuguese population are similar to other European countries.

Diagnostic Delay of Multiple Sclerosis in a Portuguese Population.

INTRODUCTION: Multiple sclerosis is a chronic inflammatory disease, in which a diagnostic delay could reduce the available therapeutic options. Therefore, it is important to monitor the time to diagnosis and understand factors that may potentially reduce it. The objective of this study was to determine the time between the first symptoms and the diagnosis of multiple sclerosis and which factors may contribute to a diagnostic delay. MATERIAL AND METHODS: Cross-sectional multicenter study, with retrospective data analysis, conducted in five tertiary Portuguese hospitals. Patients were consecutively selected from each local multiple sclerosis patients´ database. Sociodemographic and initial clinical data were collected through a questionnaire. Date of final diagnosis and multiple sclerosis classification was obtained from clinical files. RESULTS: A total of 285 patients were included with mean age at diagnosis of 36 years. The median time between first clinical manifestation and multiple sclerosis diagnosis was nine months (IQR 2 - 38). Diagnostic delay was associated with an older age (p < 0.001; r = 0.35), motor deficit at onset [26.5 months (IQR 4.5 - 56.5); p = 0.0005], higher number of relapses before diagnosis (p < 0.001; r = 0,626), first observation by other medical specialty [11 months (IQR 2 - 48); p < 0.001], prior alternative diagnosis [20 months (IQR 4 - 67.5); p < 0.001] and primary progressive subtype [37 months (IQR 25 - 64.5); p < 0.001]. The most significant delay occurred between the initial symptom and neurological observation. DISCUSSION: A significant delay occurred between initial symptoms and the diagnosis of multiple sclerosis, reflecting the need toincrease awareness of this entity and its diverse symptom presentation.

Introdução: A esclerose múltipla é uma doença inflamatória crónica na qual um atraso no diagnóstico poderá reduzir as opções terapêuticas, sendo importante monitorizar o tempo até ao diagnóstico e compreender os fatores que potencialmente o reduzam. Foi objetivo deste estudo determinar o tempo entre os primeiros sintomas e o diagnóstico de esclerose múltipla e quais os fatores que podem contribuir para o atraso no diagnóstico. Material e Métodos: Estudo multicêntrico transversal retrospetivo, realizado em cinco hospitais portugueses. Os doentes foram selecionados, consecutivamente, a partir de bases de dados locais. Os dados sociodemográficos e clínicos iniciais foram adquiridos através de questionário individual. A data do diagnóstico final e a classificação da esclerose múltipla foram obtidas por consulta do processo clínico. Resultados: Foram incluídos 285 doentes com média de idade ao diagnóstico de 36 anos. A mediana do tempo entre a primeira manifestação clínica e o diagnóstico foi de nove meses (IQR 2 - 38). O atraso no diagnóstico foi associado a idade avançada (p < 0,001; r = 0,35), défice motor inicial [26,5 meses (IQR 4,5 - 56,5), p = 0,0005], maior número de surtos previamente ao diagnóstico (p < 0,001; r = 0,626), primeira observação por outra especialidade médica [11 meses (IQR 2 - 48); p < 0,001], diagnóstico prévio alternativo [20 meses (IQR 4 - 67,5); p < 0,001] e esclerose múltipla primária progressiva [37 meses (IQR 25 - 64,5), p < 0,001]. O atraso mais significativo ocorreu entre o primeiro sintoma e a observação por neurologista. Discussão: Ocorreu um atraso significativo entre o primeiro sintoma e o diagnóstico de esclerose múltipla, refletindo uma necessidade de maior acuidade na identificação dos seus principais sintomas.

Psychoactive drugs as risk factors for functional decline among noninstitutionalized dependent elderly people.

OBJECTIVE: To analyze the association between use of psychoactive drugs and functional decline among noninstitutionalized dependent elderly people. DESIGN: Cross-sectional study. PARTICIPANTS: A total of 161 community-dwelling elderly people with functional dependence. MEASUREMENTS: The data were analyzed using logistic regression with adjustment for age models. The independent variables were the following: use of psychoactive drugs (antidepressants, anticonvulsants, anxiolytics, antipsychotics, or sedatives), cognitive decline (Mini-Mental State Examination score<20), and daytime sleepiness. The dependent variables were the following: dependence relating to activities of daily living (ADLs) and dependence relating to instrumental activities of daily living (IADLs). RESULTS: Data on 131 individuals of mean age 77.5 years were analyzed. Psychoactive drugs were used by 33.6%. Age-adjusted univariate analysis showed associations between psychoactive drug use and both ADLs and IADLs. However, in multivariate analysis, only ADLs showed a significant association with psychoactive drug use, independent of cognitive decline and daytime sleepiness (OR=2.67; 95% CI: 1.04-6.85; P=.04). CONCLUSIONS: There is a greater risk of impairment of ADLs among noninstitutionalized elderly people using psychoactive drugs. These results indicate the need for rational use of medication groups among this population with greater risk of functional impairment.

[Guillain-Barré syndrome]. / Síndrome de Guillain-Barré

Guillain-Barré syndrome (GBS) is an autoimmune disease that leads to an axonal demyelination and/or degeneration of peripheral nerves through molecular mimicry. The usual pattern is an ascending areflexic motor paralysis with a distinct cerebral-spinal fluid (CSF) showing elevated protein level without accompanying pleocytosis. Diagnosis is essentially clinical, but the CSF studies and electrodiagnostic features may help confirming the diagnosis. Prognosis is usually good, with complete recovery in 80-85% of the cases. However, 10% will remain with permanent neurological damage and about 5% will die. Immunomodulation is the goal treatment, but supportive care is of the utmost importance in the treatment and prevention of complications. The purpose of this work was to review all GBS diagnosed between 1st January 1997 and 31st December 2001, in patients 18 or older admitted to Hospital Pedro Hispano (Portugal). During the 5-year study period, 62446 patients were admitted to hospital, of which 15 with GBS. Thirteen had a good evolution: 10 with total recovery over a period of a maximum of six months; one remain with serious neurological damage at 2 years of evolution and the remaining one died with a pure motor form of GBS (both had a previous gastrointestinal infection). The results of this review are in accordance with what is described in the literature, regarding incidence, epidemiological data and clinical behaviour.