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ABSTRACT In recent years, the diagnostic accuracy of Alzheimer’s disease has been enhanced by the development of different types of biomarkers that indicate the presence of neuropathological processes. In addition to improving patient selection for clinical trials, biomarkers can assess the effects of new treatments on pathological processes. However, there is concern about the indiscriminate and poorly supported use of biomarkers, especially in asymptomatic individuals or those with subjective cognitive decline. Difficulties interpreting these tests, high costs, and unequal access make this scenario even more challenging in healthcare. This article presents the recommendations from the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology (Departamento Científico de Neurologia Cognitiva e Envelhecimento da Academia Brasileira de Neurologia) regarding the rational use and interpretation of Alzheimer’s disease biomarkers in clinical practice. The clinical diagnosis of cognitive-behavioral syndrome is recommended as the initial step to guide the request for biomarkers.

ABSTRACT Novel therapies for Alzheimer’s disease, particularly anti-amyloid drugs like lecanemab and donanemab, have shown modest clinical benefits but also significant risks. The present paper highlights the challenges of access to diagnosis, cost-effectiveness, safety, and the need for more representation of diverse populations in clinical trials. Recommendations include careful patient selection, risk-benefit analysis, and the importance of proven amyloid pathology for treatment. Future work involves further research on anti-amyloid therapies in Brazil and the development of more effective treatments for Alzheimer’s disease.

Background Infectious meningoencephalitis is a potentially fatal clinical condition that causes inflammation of the central nervous system secondary to the installation of different microorganisms. The FilmArray meningitis/encephalitis panel allows the simultaneous detection of 14 pathogens with results in about one hour.

Introdução: O teste de metagenômica RNA em amostras de líquido cefaloraquidiano (LCR) foi recentemente incorporado no laboratório clínico e vem ganhando força como uma ferramenta diagnóstica importante na prática médica. A técnica realiza a pesquisa e genotipagem do material genético (RNA) de patógenos presentes nas amostras através de amplificação randômica seguido de sequenciamento de nova geração (NGS) e análise bioinformática. Métodos: Levantamento dos resultados de 102 exames realizados no período de janeiro de 2020 a agosto de 2021, consultando os laudos no sistema informatizado da Instituição. Os dados foram avaliados quanto a positividade e patógenos detectados. Resultados: Observamos uma taxa de positividade no teste de 11% no período, sendo o HIV1 o vírus mais frequentemente encontrado. A técnica permite também identificar outros patógenos através da detecção do RNA mensageiro de vírus DNA, bactérias, fungos, protozoários e helmintos, que são liberados como achados incidentais. Esses outros patógenos foram encontrados em 5,89% dos pacientes testados. Em um desses casos, foi encontrado material genético do patógeno Spirometra erinaceieuropaei, um parasita de humanos e animais domésticos da classe Cestoda. Há relatos na literatura de que este organismo pode causar a doença infecciosa conhecida como Esparganose em sistema nervoso central (SNC). Conclusão: O diagnóstico de infecções virais muitas vezes é dificultado pela elevada diversidade genética dos vírus e também pelo surgimento de novos patógenos que não são detectados por métodos tradicionais de sorologia ou moleculares via PCR. Sendo assim, essa nova metodologia auxilia a conduta clínica nesses pacientes com quadros inespecíficos e cada vez mais vem ganhando espaço na prática médica.

Background: Previous reported neurologic sequelae associated with SARS-CoV-2 infection have mainly been confined to hospital-based patients in which viral detection was restricted to nasal/throat swabs or to IgM/IgG peripheral blood serology. Here we describe seven cases from Brazil of outpatients with previous mild or moderate COVID-19 who developed subacute cognitive disturbances.Methods: From June 1 to August 15, 2020, seven individuals 18 to 60 years old, with confirmed mild/moderate COVID-19 and findings consistent with encephalopathy who were observed >7 days after respiratory symptom initiation, were screened for cognitive dysfunction. Paired sera and CSF were tested for SARS-CoV-2 (IgA, IgG ELISA, and RT-PCR). Serum and intrathecal antibody dynamics were evaluated with oligoclonal bands and IgG index. Cognitive dysfunction was assessed by the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and the Clock Drawing Test (CDT).Results: All but one of our patients were female, and the mean age was 42.6 years. Neurologic symptoms were first reported a median of 16 days (IQR 15–33) after initial COVID-19 symptoms. All patients had headache and altered behavior. Cognitive dysfunction was observed mainly in phonemic verbal fluency (MoCA) with a median of six words/min (IQR 5.25–10.75) and altered visuospatial construction with a median of four points (IQR 4–9) (CDT). CSF pleocytosis was not detected, and only one patient was positive for SARS-CoConclusions: A subacute cognitive syndrome suggestive of SARS-CoV-2-initiated damage to cortico-subcortical associative pathways that could not be attributed solely to inflammation and hypoxia was present in seven individuals with mild/moderate COVID-19.

ABSTRACT The diagnosis of multiple sclerosis (MS) has changed over the last decade, but remains a composite of clinical assessment and magnetic resonance imaging to prove dissemination of lesions in time and space. The intrathecal synthesis of immunoglobulin may be a nonspecific marker and there are no plasma biomarkers that are useful in the diagnosis of MS, presenting additional challenges to their early detection. Methods We performed a preliminary untargeted qualitative lipidomics mass spectrometry analysis, comparing cerebrospinal fluid (CSF) and plasma samples from patients with MS, other inflammatory neurological diseases and idiopathic intracranial hypertension. Results Lipid identification revealed that fatty acids and sphingolipids were the most abundant classes of lipids in the CSF and that glycerolipids and fatty acids were the main class of lipids in the plasma of patients with MS. The area under the curve was 0.995 (0.912–1) and 0.78 (0.583–0.917), respectively. The permutation test indicated that this ion combination was useful for distinguishing MS from other inflammatory diseases (p < 0.001 and 0.055, respectively). Conclusion This study concluded that the CSF and plasma from patients with MS bear a unique lipid signature that can be useful as a diagnostic biomarker.

ABSTRACT The cytological and biochemical examination of cerebrospinal fluid (CSF) has been used for the presumed diagnosis of bacterial meningitis until the final microbiological results are achieved. We assessed the ability of CSF lactate in comparison with other CSF parameters to discriminate bacterial and enteroviral community acquired meningitis. We included 1,187 CSF samples of acute community-acquired meningitis, being 662 cases of bacterial and 525 of enteroviral meningitis. Lactate concentration (mg/dL), leukocyte count/mm3, protein (mg/dL), and glucose (mg/dL) were compared between bacterial and viral meningitis. Receiver operator characteristic (ROC) curves were used to assess diagnostic performance. CSF leukocytes, CSF protein and CSF lactate were significantly higher in bacterial meningitis cases (P

IntroductionInfiltration of the central nervous system (CNS) by hematologic or lymphoid malignant cells can cause extensive neurological damage, be progressive and fatal. However, usually, the cerebrospinal fluid (CSF) has low cellularity and rapid cell degeneration, which can impair cytometry analysis. Storage and transport measures, sample preparation, and staining protocols can interfere with diagnostic accuracy.ObjectiveTo calculate the diagnostic performance of flow cytometry (FC) using a cell stabilizer for sample preservation compared to cytomorphology in the detection of CNS infiltration by lymphoid and hematologic neoplasms.MethodsCell samples from all consecutive patients with suspected infiltration by hematological malignancies evaluated between January 2014 and December 2016 were included. Cases were analyzed by FC using a cell preservation medium and cytomorphology. Sensitivity and specificity were calculated.ResultsFrom 414 CSF samples, 72 had a phenotype compatible with characteristics of infiltration by hematological disease, whereas cytology was positive for 35 cases. FC showed higher sensitivity and specificity when compared to cytomorphology, particularly in cases with cellularity under 5 leukocytes/mm3.ConclusionWe demonstrated that collecting CSF in a medium that preserves the stability of the sample improves accuracy when compared to cytomorphology, particularly in low-volume and low-cellularity samples.

The central nervous system demyelinating diseases are a group of disorders with different etiologies, characterized by inflammatory lesions that are associated with loss of myelin and eventually axonal damage. In this group the most studied ones are multiple sclerosis (MS), neuromyelitis optic (NMO) and acute disseminated encephalomyelitis (ADEM). The cerebrospinal fluid is essential to differentiate between these different syndromes and to define multiple sclerosis, helping to assess the probability of Clinical Isolated Syndrome turn into multiple sclerosis.

This study was thought to characterized clinical and laboratory findings of a narcoleptic patients in an out patients unit at São Paulo, Brazil. METHOD: 28 patients underwent polysomnographic recordings (PSG) and Multiple Sleep Latency Test (MSLT) were analyzed according to standard criteria. The analysis of HLADQB1*0602 allele was performed by PCR. The Hypocretin-1 in cerebral spinal fluid (CSF) was measured using radioimmunoassay. Patients were divided in two groups according Hypocretin-1 level: Normal (N) - Hypocretin-1 higher than 110pg/ml and Lower (L) Hypocretin-1 lower than 110 pg/ml. RESULTS: Only 4 patients of the N group had cataplexy when compared with 14 members of the L group (p=0.0002). DISCUSSION: This results were comparable with other authors, confirming the utility of using specific biomarkers (HLA-DQB1*0602 allele and Hypocretin-1 CSF level) in narcolepsy with cataplexy. However, the HLADQB1*0602 allele and Hypocretin-1 level are insufficient to diagnose of narcolepsy without cataplexy.Este estudo foi idealizado para avaliar as características clinicas e laboratoriais de uma população de narcolépticos atendidos num centro de referência na cidade de São Paulo (Brasil). MÉTODO: 28 pacientes realizaram polissonografia e teste de múltiplas latências do sono segundo critérios internacionais. O alelo HLADQB1*0602 foi identificado por PCR. A Hipocretina-1 no líquido cefalorradiano (LCR) foi mensurada por radioimunoensaio. Os pacientes foram divididos em 2 grupos conforme o nível de Hipocretina-1. Normal (N) - Hypocretin-1 >110pg/ml e baixa (B) - Hypocretina-1

ABSTRACT The cerebrospinal fluid analysis has been employed for supporting multiple sclerosis diagnosis and ruling out the differential diagnoses. The most classical findings reflect the inflammatory nature of the disease, including mild pleocytosis, mild protein increase, intrathecal synthesis of immunoglobulin G, and, most typically, the presence of oligoclonal bands. In recent years, new biomarkers have emerged in the context of multiple sclerosis. The search for new biomarkers reflect the need of a better evaluation of disease activity, disease progression, and treatment efficiency. A more refined evaluation of disease and therapy status can contribute to better therapeutic choices, particularly in escalation of therapies. This is very relevant taking into account the availability of a greater number of drugs for multiple sclerosis treatment in recent years. In this review, we critically evaluate the current literature regarding the most important cerebrospinal fluid biomarkers in multiple sclerosis. The determination of biomarkers levels, such as chemokine ligand 13, fetuin A, and mainly light neurofilament has shown promising results in the evaluation of this disease, providing information that along with clinical and neuroimaging data may contribute to better therapeutic decisions.

ABSTRACT Multiple sclerosis (MS) is an autoimmune, inflammatory, and degenerative disease of the central nervous system. Axonal degeneration is triggered by inflammation and is the pathological substrate of progressive disability in patients with MS. Therapeutic interventions can reduce inflammatory activity, thus delaying neurodegeneration and the progression of disability. Disease activity and neurodegeneration are assessed mainly through clinical evaluation and magnetic resonance imaging. These measures lack sensitivity and accuracy, so new biomarkers are necessary. Several markers have been studied and to date the most promising is neurofilament light (NfL), a component of the axonal cytoskeleton, which is released into cerebrospinal fluid (CSF) following axonal damage. In the present study, we review the current knowledge about CSF NfL determination in MS, clinically isolated syndrome, and radiologically isolated syndrome, and critically discuss how CSF NfL measurement may contribute to therapeutic decision-making in these patients.