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The presence of central nervous system lesions fulfilling the criteria of dissemination in space and time on MRI leads to the diagnosis of a radiologically isolated syndrome (RIS), which may be an early sign of multiple sclerosis (MS). However, some patients who do not fulfill the necessary criteria for RIS still evolve to MS, and some T2 hyperintensities that resemble demyelinating lesions may originate from mimics. In light of the recent recognition of the efficacy of disease-modifying therapy (DMT) in RIS, it is relevant to consider additional imaging features that are more specific of MS. We performed a narrative review on cortical lesions (CL), the central vein sign (CVS), and paramagnetic rim lesions (PRL) in patients with RIS. In previous RIS studies, the reported prevalence of CLs ranges between 20.0 and 40.0%, CVS + white matter lesions (WMLs) between 87.0 and 93.0% and PRLs between 26.7 and 63.0%. Overall, these imaging findings appear to be frequent in RIS cohorts, although not consistently taken into account in previous studies. The search for CLs, CVS + WML and PRLs in RIS patients could lead to earlier identification of patients who will evolve to MS and benefit from DMTs.
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Esclerosis Múltiple , Humanos , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/tratamiento farmacológico , Esclerosis Múltiple/patología , Imagen por Resonancia Magnética/métodos , Enfermedades Desmielinizantes/diagnóstico por imagen , Enfermedades Desmielinizantes/tratamiento farmacológico , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patologíaRESUMEN
BACKGROUND: Pediatric-onset multiple sclerosis (POMS) accounts for 3 to 10% of all MS diagnoses. POMS is usually characterized by prominent disease activity, and patients are at higher risk of developing physical disability and cognitive impairment. OBJECTIVE: This article characterizes a cohort of POMS patients followed at the pediatric neurology unit of a Portuguese tertiary hospital. METHODS: Retrospective observational study. Clinical records of all patients with POMS between 2011 and 2020 were revised. RESULTS: A total of 21 patients, with a female:male ratio of 11:10 and a mean age of onset of 14.8 years were included. Clinical manifestations at presentation included myelitis in eight patients (two with associated brainstem syndrome), optic neuritis in six (one with associated cerebellar syndrome), supratentorial symptoms in four, and isolated brainstem syndrome in two. Twenty patients had oligoclonal immunoglobulin G bands in cerebrospinal fluid. Supra- and infratentorial involvement was identified in the first brain magnetic resonance imaging of nine patients. Initial relapses were treated with intravenous steroids in 19 patients. The mean time for diagnosis was 2.8 months. Eleven patients were on first-line treatment (nine on ß-interferon, two on teriflunomide) and 10 on second-line treatment (six on natalizumab, three on fingolimod, one on ocrelizumab). The mean annual relapse rate was 0.29 (range, 0.01-3), and the median Expanded Disability Status Scale was 1. Four patients reported learning disabilities and/or cognitive deficits. CONCLUSION: About half of patients in this cohort were on second-line disease-modifying treatment, with 19% showing cognitive impairment. Efforts to establish an early diagnosis are crucial to improving these patients' outcomes.
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Esclerosis Múltiple , Niño , Humanos , Masculino , Femenino , Adolescente , Esclerosis Múltiple/diagnóstico por imagen , Centros de Atención Terciaria , Encéfalo , Interferón beta/uso terapéutico , Tronco EncefálicoRESUMEN
Objectives. Immune reconstitution therapies (IRT), which include antibody-based cell-depleting therapies targeting CD52+ (alemtuzumab) or CD20+ (rituximab, ocrelizumab) leukocytes, are approved for the treatment of multiple sclerosis. Thyroid autoimmunity is a common adverse effect of alemtuzumab treatment, Graves' disease (GD) being the most prevalent manifestation. To date, thyroid autoimmunity events have not been reported with CD20-targeting monoclonal antibodies. Case Report. A 59-year-old woman with primary progressive multiple sclerosis with no prior personal history of thyroid disease or autoimmunity, was diagnosed with GD 6 months following the first ocrelizumab infusion. She was asymptomatic and had no signs of ophthalmopathy. Due to the temporal association of GD diagnosis with ocrelizumab infusion, absence of symptoms and our experience with alemtuzumab-induced GD, we decided for an active surveillance strategy and antithyroid drugs were not started. She underwent spontaneous resolution of hyperthyroidism with thyroid-stimulating hormone (TSH) receptor antibodies (TRAb) negativity and a mild and transitory period of subclinical hypothyroidism, while she continued the biannually ocrelizumab administration schedule. To present date, she has maintained close clinical and biochemical surveillance with normal TSH, free thyroxine (fT4) and free triiodothyronine (fT3) levels and undetectable TRAb. Conclusions. This is the first case of GD reported after ocrelizumab administration. The timing, onset and course of this case is similar to alemtuzumab-induced GD, usually interpreted as an "immune reconstitution syndrome"; however, ocrelizumab cell count depletion is inferior in severity, cell population affected and duration of depletion. This case highlights the importance of pre-screening and follow-up with thyroid function tests in patients treated with ocrelizumab. As a novel therapeutic antibody, further investigation is required to unravel the causes of thyroid autoimmunity.
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Enfermedad de Graves , Esclerosis Múltiple Crónica Progresiva , Esclerosis Múltiple , Anticuerpos Monoclonales Humanizados , Femenino , Enfermedad de Graves/tratamiento farmacológico , Humanos , Persona de Mediana Edad , Esclerosis Múltiple/tratamiento farmacológico , Esclerosis Múltiple Crónica Progresiva/tratamiento farmacológicoRESUMEN
INTRODUCTION: Some myasthenia gravis (MG) patients are refractory to conventional treatments. METHODS: To describe the clinical features of refractory MG (RMG) and explore the association with human leukocyte antigen HLA-DRB1 alleles, a cohort study of 114 consecutive MG patients was performed. Patients were classified as RMG based on predefined criteria. RESULTS: Twenty-two patients were found to have RMG (19.3%). There were no differences between non-RMG and RMG patients with respect to sex, age of onset, abnormal 3-Hz repetitive nerve stimulation, anti-acetylcholine receptor antibody positivity, thymectomy, thymoma or thymic hyperplasia, and polyautoimmunity. HLA-DRB1*03 was more frequent in the non-RMG vs. control population (P = 3 × 10-6 ). The HLA-DRB1*13 allele was less frequent in non-RMG patients compared with controls (P = 0.002), and less frequent in the non-RMG group compared with the RMG group (P = 0.003). DISCUSSION: HLA-DRB1*03 was more common in non-RMG, and the HLA-DRB1*13 allele appeared to have a protective role, as reported previously in other autoimmune disorders. Muscle Nerve 60: 188-191, 2019.
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Cadenas HLA-DRB1/genética , Miastenia Gravis/genética , Adulto , Edad de Inicio , Autoanticuerpos/inmunología , Estudios de Casos y Controles , Estudios de Cohortes , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Miastenia Gravis/epidemiología , Miastenia Gravis/inmunología , Portugal/epidemiología , Factores Protectores , Receptores Colinérgicos/inmunología , Timectomía/estadística & datos numéricos , Timoma/epidemiología , Hiperplasia del Timo/epidemiología , Neoplasias del Timo/epidemiología , Adulto JovenRESUMEN
BACKGROUND: Hypertrophic pachymeningitis (HP) is characterized by cranial and/or spinal thickening of the dura mater with or without associated inflammation. Neuroimaging studies reveal dura mater thickening and focal or diffuse contrast enhancement. It is described in association with trauma, infections, tumors, autoimmune/inflammatory diseases, and cerebrospinal fluid hypotension syndrome, with some cases remaining idiopathic. METHODS: A retrospective study was conducted with patients' identification through a key terms search within MRI reports in the period of July 2008 to September 2015. Clinical files, MRI, laboratory, and pathology data were reviewed. RESULTS: Fifty-three patients were identified and 20 were excluded because they did not meet the inclusion criteria. Of the 33 included, 19 were female, with a mean age at symptoms onset of 51.2 ± 17.6 years. The most common presenting symptoms were headache and cranial nerves palsy, followed by seizures, delirium, lumbar pain, cognitive decline, motor deficit, and language impairment. In 17 patients, a neoplastic etiology was identified; in eight, inflammatory/autoimmune; in six, infectious; and two were classified as idiopathic. Of the eight patients with inflammatory/autoimmune etiology, four had possible IgG4-related disease (IgG4-RD) and the remaining had granulomatosis with polyangiitis, sarcoidosis, rheumatoid arthritis, and Tolosa-Hunt syndrome. Treatment was directed according to the underlying etiology. DISCUSSION: In the described series, a female predominance was identified, with symptoms' onset in the 5th decade. Although headache was the most common symptom, clinical presentation was varied, emphasizing the role of MRI in HP diagnosis. The underlying etiologies were diverse, with only a few cases remaining idiopathic, also reflecting the contribution of the recently described IgG4-RD.
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Encefalitis/etiología , Imagen por Resonancia Magnética , Meningitis/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Diagnóstico Diferencial , Encefalitis/diagnóstico por imagen , Femenino , Encuestas Epidemiológicas , Humanos , Hipertrofia/complicaciones , Procesamiento de Imagen Asistido por Computador , Masculino , Meningitis/complicaciones , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
INTRODUCTION: In this study we estimated the prevalence, incidence, and mortality of myasthenia gravis (MG) in northern Portugal and characterized the clinical features of the patients identified. METHODS: We used 2 data sources: clinical records from the hospitals and pyridostigmine prescription registers. RESULTS: On December 31, 2013, we estimated a point prevalence of 111.7 patients per million population. The highest prevalence was observed in the group >65 years of age, especially in men (288.1 per million). During 2013, we estimated an incidence rate of 6.3 per million per year. Among women, the incidence rate was highest in the 15-49-year age group; in men, incidence increased with age up to 22.1 per million in those >65 years old. The MG-related mortality rate was 0.5 per million. CONCLUSIONS: These figures are in keeping with similar studies and emphasize the importance of diagnosis and management of MG in elderly populations. Muscle Nerve 54: 413-421, 2016.
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Miastenia Gravis/epidemiología , Adolescente , Adulto , Distribución por Edad , Anciano , Anticuerpos/sangre , Niño , Preescolar , Bases de Datos Factuales , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Miastenia Gravis/sangre , Examen Neurológico , Portugal/epidemiología , Prevalencia , Proteínas Tirosina Quinasas Receptoras/inmunología , Receptores Colinérgicos/inmunología , Estudios Retrospectivos , Adulto JovenRESUMEN
Background: Anti-titin antibodies have been previously associated with thymoma-associated myasthenia gravis (MG) and a more clinically severe form of MG. While currently only serving as a disease biomarker, its possible utility as an indicator of underlying thymus malignancy may be of value in clinical practice. Methods: Data was retrospectively collected and analyzed from 2013 to 2022 using an institutional record of MG patients. Anti-titin antibodies were assessed using Line Blot immunoassay. Results: From 130 MG cases, 32 (24.6%) were anti-titin positive. Anti-titin positive cases were associated with older age of disease onset [median (IQR): 63.0 (44.3-70.8) vs. 35.5 (24.8-60.8) years] (P<0.01). Thymectomy was performed in 46 (35.4%) MG patients, 12 of which anti-titin positive (26.1%). Thymectomy samples from anti-titin positive patients comprised 10 (83.3%) cases of thymoma and 2 (16.7%) cases of thymus hyperplasia. There was a tendency towards anti-titin positive patients having more thymoma while anti-titin negative displayed more hyperplasia (P<0.01). Anti-titin positivity correlated with thymoma in patients with age of onset bellow 50 years (P=0.028). Anti-titin positivity was significantly associated with generalized MG in the late-onset group (P=0.005). Conclusions: The presence of anti-titin antibodies appears to correlate with underlying thymoma in early-onset MG cases and with generalized MG in late-onset cases. Prospective studies are needed to further study this association.
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BACKGROUND: Central nervous system dysfunction is common in longstanding hereditary transthyretin amyloidosis (ATTRv) caused by the V30M (p.V50M) mutation. Neuropathology studies show leptomeningeal amyloid deposition and cerebral amyloid angiopathy (CAA). Brain MRI is widely used in the assessment of Aß associated CAA but there are no systematic studies with brain MRI in ATTRv amyloidosis. METHODS: we performed 3 T brain MRIs in 16 patients with longstanding (>14 years) ATTRV30M. We additionally retrospectively reviewed 48 brain MRIs from patients followed at our clinic. CNS symptoms and signs were systematically accessed, and MRIs were blindly reviewed for ischaemic and haemorrhagic lesions. RESULTS: in the prospective cohort, we found white matter hyperintensities in 8/16 patients (50%, Fazekas score> =1). There were no relevant microbleeds, large ischaemic or haemorrhagic lesions or superficial siderosis. In the retrospective cohort, microbleeds were found in 5/48 patients (10,4%), two of which with > =20 microbleeds. White matter hyperintensities were found in 20/48 cases (41.7%). White matter lesions, microbleeds and cortical atrophy were not associated with disease duration. CONCLUSIONS: white matter hyperintensities are common in ATTRV30M, irrespective of disease duration. Haemorrhagic lesions are rare, even in patients with longstanding disease, suggesting the existence of other risk factors.
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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.
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Glicoproteína Mielina-Oligodendrócito , Neuromielitis Óptica , Sistema de Registros , Humanos , Neuromielitis Óptica/epidemiología , Femenino , Masculino , Portugal/epidemiología , Adulto , Pronóstico , Persona de Mediana Edad , Glicoproteína Mielina-Oligodendrócito/inmunología , Estudios de Cohortes , Progresión de la Enfermedad , Autoanticuerpos/sangre , Personas con Discapacidad , Evaluación de la Discapacidad , Acuaporina 4/inmunología , Adulto Joven , Estudios de Seguimiento , Anciano , RecurrenciaRESUMEN
INTRODUCTION/BACKGROUND: Idiopathic Inflammatory Myopathies (IIM) continue to be a major clinical challenge worldwide. The exact aetiopathogenesis of this chronic and disabling disease remains elusive, preventing the development of novel and effective therapeutic strategies and leading to a high incidence of damage. The complexity of treating these diseases is even greater due to the numerous comorbidities that affect these patients. METHODS: Retrospective review of the cohort of patients diagnosed with IIM and followed in a dedicated unit of a tertiary hospital between 1971 and December 2022, with particular attention to damage and comorbidities. Damage was assessed using the Myositis Damage Index. Comorbidities were recorded and analysed as a whole and also assessed using the Charlson Comorbidity Index. Health Assessment Questionnaire (HAQ) Disability Index (DI) was performed by phone call in December 2022, to all patients actively followed-up in the Unit. RESULTS: Analysis of 149 patients with a mean follow-up of 9 years (range 0-51) revealed >90% with damage and comorbidities. Most comorbidities were a consequence of the damage and were particularly related to prolonged steroid therapy. Cardiovascular damage, which occurred either as cardiovascular risk factors or as end-organ sequelae (cardiovascular disease and chronic kidney disease), was the main cause and a major contributor to death. Depression was also high on the list of associated comorbidities. Median HAQ was 2.09 representing high negative impact in quality of life. CONCLUSIONS: Although survival rates have increased in recent decades, patients with IIM carry a high burden of disease with poor quality of life, mainly caused by damage and comorbidities. While comorbidities accumulation is the major factor for poor quality of life, damage severity is the main predictor for mortality. Improved therapeutic strategies are needed to reduce the need for steroids and to introduce routine screening and management of comorbidities as an essential partner of immunosuppressive therapy, leading to comprehensive care of myositis patients and effective improvement of their quality of life.
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Miositis , Calidad de Vida , Humanos , Miositis/patología , Estudios de Cohortes , Comorbilidad , Costo de EnfermedadRESUMEN
Teriflunomide is an oral disease-modifying therapy for relapsing-remitting multiple sclerosis patients. A decline in physical and cognitive functions, which negatively impacts their quality of life (QoL), is observed in relapsing-remitting multiple sclerosis patients. The aim of this study was to characterise adult Portuguese relapsing-remitting multiple sclerosis patients treated with teriflunomide in routine clinical practice concerning their quality of life, comorbidities, treatment effectiveness, satisfaction, compliance and safety. TeriLIVE-QoL was a multicentre, non-interventional, prospective cohort study that collected demographic and clinical characteristics, patient-reported outcomes and adverse events from patients treated with teriflunomide of 14 mg over 2 years. Notably, around 18 months of this period occurred during the COVID-19 pandemic. Of the 99 participants, 25% were treatment-naïve. Annualised relapse rate and the score for the Hospital Anxiety and Depression Scale decreased after 1 (p = 0.01) and 2 years of treatment (p < 0.001), respectively. Convenience (p = 0.001), effectiveness (p = 0.002) and global satisfaction scores (p < 0.001) presented high values (up to 95.6) and continued to improve along the study. Treatment persistence was 77%, and compliance reached 82% 2 years after initiation. Three patients experienced serious adverse events. TeriLIVE-QoL provides real-world evidence of clinical effectiveness, high treatment satisfaction, consistent safety and improved psychiatric outcomes, associated with elevated treatment persistence and compliance in patients treated with teriflunomide.iance reached 82% 2 years after initiation. Three patients experienced serious adverse events.
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BACKGROUND: Late-onset multiple sclerosis (LOMS) is defined as the onset of symptoms above 50 years, corresponding to an increasingly recognized subset of MS. This study aimed at comparing demographic and clinical data of patients with LOMS to those of early-onset MS (EOMS) from a Portuguese cohort. METHODS: Retrospective chart review of an MS cohort from a Portuguese tertiary center. RESULTS: From 746 patients with MS (61.7% female), we identified 39 cases with presentation after 50 years of age (22 males and 17 females), corresponding to 5.3%. The mean age at onset was 55.4 (±5.0) for LOMS and 29.5 (±8.9) for EOMS. There was no significant difference in disease duration. The most common type was relapsing-remitting MS, accounting for 51.5% and 83.9% of LOMS and EOMS patients, respectively. Primary-progressive MS (PPMS) was significantly more represented in the LOMS group (41.0%) (p < 0.01). The median EDSS was significantly higher in the LOMS group (4.75, 0.0-7.5) when compared to the EOMS group (2.0, 0.0-9,0). The most frequent presenting feature was myelitis in both LOMS (48.7%) and EOMS patients (47.4%), resulting in significantly higher EDSS (p = 0.003). CONCLUSIONS: LOMS is associated with higher EDSS when considering the same disease duration, translating into increased disability.
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Esclerosis Múltiple Recurrente-Remitente , Esclerosis Múltiple , Masculino , Humanos , Femenino , Esclerosis Múltiple/diagnóstico , Estudios Retrospectivos , Portugal , Edad de Inicio , Progresión de la EnfermedadRESUMEN
INTRODUCTION: Anti-contactin-associated protein-like 2 (CASPR2) is classically associated with limbic encephalitis (LE), Morvan syndrome and peripheral nerve hyperexcitability (PNH). Additional clinical features have been previously recognized. OBJECTIVE: To describe a cohort of patients with anti-CASPR2-associated neurological syndromes from a tertiary referral centre. METHODS: Retrospective analysis of patients with positive serum anti-CASPR2 antibodies in the period between 2014 and 2021. RESULTS: Nineteen patients were identified, 11 (57.9%) male, with a median age at symptom onset of 49.0 (31.3-63.0) years and a median time to diagnosis of 1.0 (0.0-1.8) years. The most common clinical syndromes were LE (7 cases, 36.8%), Morvan syndrome (4, 21.1%) and PNH (2, 10.5%). Six patients presented with atypical phenotypes (31.6%), comprising dysautonomia (orthostatic hypotension and Adie's Pupil), motor tics/stereotypies, obsessive-compulsive disorder, and brainstem involvement. The most common presenting symptoms were seizures (31.6%), PNH (21.1%) and cognitive dysfunction (15.8%). One LE patient had a disease duration of 2,5 years and was initially diagnosed with dementia. CSF was normal in most cases. Brain MRI showed temporal lobe hyperintensities in 4 LE cases (57.1%). All PNH cases had myokymic discharges of fasciculations in the electromyography. Two patients had associated thymoma and 1 had lung adenocarcinoma. Eight patients (42.1%) received treatment during the acute phase and 26.3% maintenance treatment. Approximately half of the treated cases improved or stabilised, with 4 (21.1%) deaths in the whole cohort. CONCLUSION: Anti-CASPR2-associated neurological disorders may present with isolated atypical phenotypes, a slowly progressive clinical course, and with normal CSF or imaging findings.
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Autoanticuerpos , Encefalitis Límbica , Femenino , Humanos , Masculino , Encefalitis Límbica/diagnóstico , Encefalitis Límbica/tratamiento farmacológico , Estudios Retrospectivos , Convulsiones/complicaciones , SíndromeRESUMEN
OBJECTIVE: The Brief Smell Identification Test (B-SIT) was used to explore odour identification capacities in multiple sclerosis (MS). METHODS: In total, 153 consecutive patients with MS and 165 healthy controls (HC) participated in the study. All participants were asked to answer the B-SIT and the Hospital Anxiety and Depression Scale (HADS). The Expanded Disability Status Scale (EDSS), the Multiple Sclerosis Severity Scale (MSSS), and the Mini-Mental State Examination (MMSE) were used for patients' clinical and cognitive characterization. RESULTS: Patients with MS (11.1%) were more impaired on the B-SIT than HC participants (3%). The frequency of impairment was higher for patients with secondary progressive (SPMS; 11/16, 68.8%) than relapsing-remitting (RRMS; 4/121, 3.3%) or primary progressive (2/16, 12.5%) courses. A threshold score of ≤ 8 on the B-SIT provided a sensitivity of 69% and a specificity of 97% in the identification of SPMS among patients with relapsing onset. The association between SPMS and impaired B-SIT remained statistically significant after adjusting for demographic (i.e. age and education), clinical (i.e. disease duration, EDSS, and MSSS), psychopathological (i.e. HADS anxiety and depression scores), and cognitive (i.e. MMSE) variables. CONCLUSIONS: A brief odour identification measure provided a good discrimination between SPMS and RRMS courses. A systematic assessment of olfactory functions may contribute to the development of clinical markers of SPMS.
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Esclerosis Múltiple Crónica Progresiva/fisiopatología , Esclerosis Múltiple Recurrente-Remitente/fisiopatología , Odorantes , Vías Olfatorias/fisiopatología , Olfato , Adolescente , Adulto , Anciano , Distribución de Chi-Cuadrado , Cognición , Diagnóstico Diferencial , Evaluación de la Discapacidad , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple Crónica Progresiva/diagnóstico , Esclerosis Múltiple Crónica Progresiva/psicología , Esclerosis Múltiple Recurrente-Remitente/diagnóstico , Esclerosis Múltiple Recurrente-Remitente/psicología , Oportunidad Relativa , Portugal , Valor Predictivo de las Pruebas , Escalas de Valoración Psiquiátrica , Estudios Retrospectivos , Umbral Sensorial , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
Despite the existence of well-established diagnostic criteria for autoimmune encephalitis, there are diseases capable of mimicking it. This study sought to retrospectively evaluate the reasons for testing and the final diagnosis of patients admitted to a Neurology ward tested for anti-NMDAR antibodies and estimate sensitivity and specificity of current diagnostic criteria. The threshold for testing was lower than that of the prevailing diagnostic criteria, and the proportion of autoimmune encephalitis mimics was high. Searching for alternative diagnoses is of pivotal importance in cases of autoimmune encephalitis suspicion, and diagnostic criteria may need expanding so that no autoimmune encephalitis is missed.
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Encefalitis Antirreceptor N-Metil-D-Aspartato , Enfermedad de Hashimoto , Encefalitis Antirreceptor N-Metil-D-Aspartato/diagnóstico , Autoanticuerpos , Encefalitis , Enfermedad de Hashimoto/diagnóstico , Humanos , Receptores de N-Metil-D-Aspartato , Estudios RetrospectivosRESUMEN
INTRODUCTION: The impact of COVID-19 in patients with neuroimmunological disorders is not fully established. There is some evidence suggesting an increased risk of more severe infection associated with the use of immunosuppressors in this population. OBJECTIVE: To characterize SARS-CoV-2 infection in patients followed in the neuroimmunology outpatient clinic of a tertiary centre from the north of Portugal. METHODS: Retrospective analysis of neuroimmunological patients with PCR-proven SARS-CoV-2 infection during the observational period of 20 months. RESULTS: Ninety-one patients were infected, 68.1% female, with a mean age of 48.9±16.7 years. The median disease duration was 11.0 (IQR 6.0-19.0) years. Sixty-one patients (67.0%) had Multiple Sclerosis, of which 50 with relapsing-remitting course, 12 (13.2%) Myasthenia Gravis (MG), 6 (6.6%) Autoimmune Encephalitis and 6 (6.6%) Chronic Inflammatory Demyelinating Polyneuropathy. Seventy-six patients (83.5%) were taking disease-modifying therapy, 77.6% of which were on immunosuppressants, including anti-CD20 in 12 (13.2%). Most patients had mild COVID-19 (84.6%), with 3 cases (3.3%) of severe disease and, 7 cases (7.7%) of critical disease being reported. In total, 13 patients were hospitalized and 4 died. Patients with severe to critical disease were significantly older than patients with milder forms (69.4±21.0 versus 46.5±14.4 years, p<0.01). MG was also associated with more severe disease (p=0.02). There was no association between comorbidities or use of immunosuppressors (including anti-CD20) and COVID-19 severity. CONCLUSIONS: Greater age and MG were associated with severe or critical COVID-19. We found no association between a specific DMT, including anti-CD20, and outcome. Clinical recovery was achieved by 93.4%.
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COVID-19 , Esclerosis Múltiple , Adulto , Anciano , Antígenos CD20 , Femenino , Humanos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/terapia , Portugal/epidemiología , Estudios Retrospectivos , SARS-CoV-2 , Centros de Atención TerciariaRESUMEN
Objective: The aim of this study is to assess the peripheral immune system of newly diagnosed patients with relapsing remitting multiple sclerosis (RRMS) and compare it to healthy controls (HC). Methods: This cross-sectional study involves 30 treatment-naïve newly diagnosed patients with RRMS and 33 sex- and age-matched HC. Peripheral blood mononuclear cells were analyzed regarding: i) thymic function surrogates [T cell receptor excision circles (TRECs) and recent thymic emigrants (RTEs)]; ii) naïve and memory CD4+ and CD8+ T cells subsets; iii) T helper (Th) phenotype and chemokine receptors expression on CD8+ T cells subsets; iv) regulatory T cell (Tregs) phenotype; and exclude expression of activating/inhibitory receptors by natural killer (NK) and NKT cells. Analyses were controlled for age, sex, and human cytomegalovirus (HCMV) IgG seroprevalence. Results: Newly diagnosed patients with RRMS and HC have equivalent thymic function as determined by similar numbers of RTEs and levels of sjTRECs, DJßTRECs, and sj/DJßTREC ratio. In the CD8+ T cells compartment, patients with RRMS have a higher naive to memory ratio and lower memory cell counts in blood, specifically of effector memory and TemRA CD8+ T cells. Interestingly, higher numbers and percentages of central memory CD8+ T cells are associated with increasing time from the relapse. Among CD4+ T cells, lower blood counts of effector memory cells are found in patients upon controlling for sex, age, and anti-HCMV IgG seroprevalence. Higher numbers of CD4+ T cells (both naïve and memory) and of Th2 cells are associated with increasing time from the relapse; lower numbers of Th17 cells are associated with higher MS severity scores (MSSS). Patients with RRMS have a higher percentage of naïve Tregs compared with HC, and lower percentages of these cells are associated with higher MSSS. Percentages of immature CD56bright NK cells expressing the inhibitory receptor KLRG1 and of mature CD56dimCD57+ NK cells expressing NKp30 are higher in patients. No major alterations are observed on NKT cells. Conclusion: Characterization of the peripheral immune system of treatment-naïve newly diagnosed patients with RRMS unveiled immune features present at clinical onset including lower memory T cells blood counts, particularly among CD8+ T cells, higher percentage of naïve Tregs and altered percentages of NK cells subsets expressing inhibitory or activating receptors. These findings might set the basis to better understand disease pathogenesis.
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Esclerosis Múltiple Recurrente-Remitente , Esclerosis Múltiple , Linfocitos T CD8-positivos , Estudios Transversales , Humanos , Inmunoglobulina G , Leucocitos Mononucleares/metabolismo , Células T de Memoria , Recurrencia , Estudios Seroepidemiológicos , Linfocitos T ReguladoresRESUMEN
INTRODUCTION: Neuromyelitis optica spectrum disorders (NMOSD) are more prevalent in adulthood, with few cases reported in pediatric age (<18 years). In this group, anti-aquaporin 4 (AQP4) antibodies are less frequent, while antibodies against myelin oligodendrocyte glycoprotein (MOG) are more commonly detectable than in adults. OBJECTIVE AND METHODS: Description of pediatric NMOSD cases identified in a national multicentric NMOSD Portuguese registry. RESULTS: Twenty (11.1%) NMOSD cases were diagnosed in pediatric age. Twelve (60%) were female, with a median age of onset of 12.5 (6.8-16.5) years. The presenting feature was transverse myelitis in 10 (50%), 4 of which with simultaneous optic neuritis and 2 with concomitant brainstem syndrome. Nine patients (45%) had pleocytosis in the CSF. Six (30.0%) exhibited anti-AQP4 antibodies, 13 (65.0%) anti-MOG antibodies, and one was seronegative for both. Four anti-AQP4 antibodies-positive patients had ≥1 relapse. Most anti-MOG-positive cases were monophasic (53.8%). In the acute phase, all patients received IV methylprednisolone, nine received IVIg and four plasma exchange. One anti-AQP4-positive patient died. Ten patients (5 anti-AQP4-positive/5 anti-MOG-positive) were on maintenance immunosuppressive therapy at the time of data collection. CONCLUSION: NMOSD may present in pediatric age. It is essential to establish the diagnosis and promptly start therapy to improve the prognosis.
Asunto(s)
Neuromielitis Óptica , Acuaporina 4 , Autoanticuerpos , Niño , Femenino , Humanos , Inmunoglobulina G , Masculino , Recurrencia Local de Neoplasia , Neuromielitis Óptica/epidemiología , Neuromielitis Óptica/terapia , Portugal/epidemiología , Estudios RetrospectivosRESUMEN
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.