Misdiagnosis in multiple sclerosis in a Brazilian reference center: Clinical, radiological, laboratory profile and failures in the diagnostic process-Cohort study.

BACKGROUND: Multiple sclerosis misdiagnosis remains a problem despite the well-validated McDonald 2017. For proper evaluation of errors in the diagnostic process that lead to misdiagnosis, it is adequate to incorporate patients who are already under regular follow-up at reference centers of demyelinating diseases. OBJECTIVES: To evaluate multiple sclerosis misdiagnosis in patients who are on follow-up at a reference center of demyelinating diseases in Brazil. METHODS: We designed an observational study including patients in regular follow-up, who were diagnosed with multiple sclerosis at our specialized outpatient clinic in the Hospital of Clinics in the University of Sao Paulo, from 1996 to 2021, and were reassessed for misdiagnosis in 2022. We evaluated demographic information, clinical profile, and complementary exams and classified participants as "established multiple sclerosis," "non-multiple sclerosis, diagnosed," and "non-multiple sclerosis, undiagnosed." Failures in the diagnostic process were assessed by the modified Diagnostic Error Evaluation and Research tool. RESULTS: A total of 201 patients were included. After analysis, 191/201 (95.02%) participants were confirmed as "established multiple sclerosis," 5/201 (2.49%) were defined as "non-multiple sclerosis, diagnosed," and 5/201 (2.49%) were defined as "non-multiple sclerosis, undiagnosed." CONCLUSIONS: Multiple sclerosis misdiagnosis persists in reference centers, emphasizing the need for careful interpretation of clinical findings to prevent errors.

A Systematic Review on Anti-Yo/PCA-1 Antibody: Beyond Cerebellar Ataxia in Middle-Aged Women with Gynecologic Cancer.

Current understanding of anti-Yo/PCA1 antibody-associated cerebellar ataxia is based on case reports and small case series. Our goal was to summarize clinical features, highlighting atypical presentations and gaps of knowledge. Following the PRISMA guidelines, we systematically screened Pubmed/MEDLINE, Embase, Scopus, and Web of Science from inception to April 2022 for all case reports and series concerning anti-Yo antibody-associated cerebellar ataxia. We collected data on clinical presentation, investigation findings, and treatment outcomes. Of 379 included patients, 96% were female with gynecologic cancer (82%). Among men, 87% had an associated tumor, mainly of gastrointestinal origin. The median age was 60 years old. Pancerebellar ataxia was the main clinical feature, but extracerebellar findings were frequent during the disease course. Vertigo and imbalance can be present early in the disease course in about two thirds of patients, as a prodromal phase. Although neuroimaging usually is normal or shows cerebellar atrophy, inflammatory changes may also be present. More than half of the patients reported some improvement after immunotherapy. However, despite treatment, 84% of survivors were unable to walk unassisted on follow-up. Our study provides objective data and advances in current knowledge of anti-Yo antibody-associated cerebellar ataxia such as the description of prodromal symptoms, extracerebellar findings, and its presentations in males.

How to choose initial treatment in multiple sclerosis patients: a case-based approach.

BACKGROUND: Immunotherapy dramatically changed the natural history of multiple sclerosis (MS), which was classically associated with severe disability. Treatment strategies advocate that early control of disease activity is crucial to avoid progressive disability, and the use of high efficacy drugs may be beneficial, but safety is a concern. Choosing the disease-modifying therapy is challenging in clinical practice and should be further discussed. OBJECTIVE: To discuss the state of art of selecting the initial therapy for relapsing MS patients. METHODS: We used a case-based approach followed by clinical discussion, exploring therapeutic options in different MS settings. RESULTS: We presented clinical cases profile compatible with the use of MS therapies, classified into moderate and high efficacy. In the moderate efficacy group, we discussed interferons, glatiramer acetate, teriflunomide and dimethyl fumarate, while in the high efficacy group we discussed fingolimod, cladribine, natalizumab, ocrelizumab, alemtuzumab and ofatumumab. CONCLUSION: Advances in MS treatment are remarkable. Strong evidence supports the use of early high efficacy therapy. However, biomarkers, clinical and radiologic prognostic factors, as well as patients' individual issues, should be valued and considered for a personalized treatment decision.

How to choose initial treatment in multiple sclerosis patients: a case-based approach / Como escolher o tratamento inicial na esclerose múltipla: uma abordagem baseada em casos

ABSTRACT Background: Immunotherapy dramatically changed the natural history of multiple sclerosis (MS), which was classically associated with severe disability. Treatment strategies advocate that early control of disease activity is crucial to avoid progressive disability, and the use of high efficacy drugs may be beneficial, but safety is a concern. Choosing the disease-modifying therapy is challenging in clinical practice and should be further discussed. Objective: To discuss the state of art of selecting the initial therapy for relapsing MS patients. Methods: We used a case-based approach followed by clinical discussion, exploring therapeutic options in different MS settings. Results: We presented clinical cases profile compatible with the use of MS therapies, classified into moderate and high efficacy. In the moderate efficacy group, we discussed interferons, glatiramer acetate, teriflunomide and dimethyl fumarate, while in the high efficacy group we discussed fingolimod, cladribine, natalizumab, ocrelizumab, alemtuzumab and ofatumumab. Conclusion: Advances in MS treatment are remarkable. Strong evidence supports the use of early high efficacy therapy. However, biomarkers, clinical and radiologic prognostic factors, as well as patients' individual issues, should be valued and considered for a personalized treatment decision.

RESUMO Antecedentes: A imunoterapia mudou drasticamente a história natural da esclerose múltipla (EM), doença esta que era classicamente associada a grandes incapacidades. Sabe-se hoje que o controle precoce da atividade de doença é crucial para evitar incapacidade progressiva, e o uso de terapias de alta eficácia pode ser benéfico. Apesar disso, a segurança ainda é uma preocupação dos pacientes e médicos. A escolha da terapia modificadora da doença é um desafio na prática clínica e suas particularidades devem ser mais discutidas. Objetivo Discutir o estado da arte da seleção da terapia inicial para pacientes com EM remitente recorrente. Métodos Utilizamos uma abordagem baseada em casos clínicos, com discussão das diversas opções terapêuticas em diferentes contextos de EM. Resultados: Foram apresentados casos clínicos compatíveis com o uso das principais terapias para EM, divididas em moderada e alta eficácia. No grupo de moderada eficácia discutimos sobre os interferons, acetato de glatirâmer, teriflunomida e fumarato de dimetila enquanto que no de alta eficácia falamos sobre fingolimode, cladribina, natalizumabe, ocrelizumabe, alentuzumabe e ofatumumabe. Conclusão Os avanços no tratamento da EM são notáveis. Fortes evidências suportam que o uso de terapia de alta eficácia de forma precoce possa ser benéfica. No entanto, biomarcadores, fatores prognósticos clínicos e radiológicos, bem como questões individuais dos pacientes, devem ser valorizados e considerados para uma decisão de tratamento personalizado.