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.

Anti-Tr/DNER Antibody-Associated Cerebellar Ataxia: a Systematic Review.

Rapidly progressive cerebellar ataxia is a classical paraneoplastic neurological syndrome associated with different autoantibodies and typical demographic characteristics, extracerebellar signs, tumor association, and prognosis. Anti-Tr/anti-Delta/Notch-like epidermal growth factor-related receptor (DNER) antibody is one of the associated antibodies. Given the rarity of this condition, our current knowledge is based on case reports and small case series. In order to improve our understanding of these conditions, we conducted a systematic review of the literature. Our study followed the PRISMA reporting guidelines. Studies of patients with the presence of anti-Tr/DNER antibodies in serum or cerebrospinal fluid (CSF) were included. We extract data information related to study characteristics, demographics, clinical symptoms, tumor association, neuroimaging, and cerebrospinal fluid analysis. Out of 131 records, we analyzed 17 papers, including a total of 85 patients with anti-Tr/DNER antibody-associated cerebellar ataxia. We confirmed that this disease occurred mostly in middle-aged males. Isolated cerebellar ataxia was the most common presentation. Extracerebellar features were rare (8%). Ninety-one percent of the patients presented an associated tumor, being Hodgkin lymphoma the most common. Abnormal neuroimaging patterns included cerebellar atrophy (19%) and cerebellar hypersignal (6%). Cerebrospinal fluid was inflammatory in 64% of the patients. Oncological response was complete in 88%, but neurological prognosis was poor with only 41% of the patients presenting significant neurological improvement at the last follow up. Anti-Tr/DNER antibodies should be tested in rapid progressive cerebellar ataxia. Oncological response is excellent; however, many patients do not improve from their cerebellar ataxia.

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.