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Objective to explore the status of concentration of klotho and fibroblast growth factor 23 (FGF23) in cerebrospinal fluid (CSF) of patients with narcolepsy. Patients/methods 59 patients with narcolepsy and 17 control individuals were enrolled. We used radioimmunoassay, human klotho enzyme-linked immunosorbent assay (ELISA), human intact FGF23 ELISA and spectrophotometry to measure hypocretin-1, klotho, FGF-23 and phosphorus, respectively. T-Student Test was used to compare klotho and phosphate concentrations, Mann–Whitney U Test were used to compare FGF-23 levels between groups. ANOVA Test was used to compare klotho and phosphate CSF concentrations among narcolepsy patients with CSF hypocretin-1 110 pg/ml (HCRT+) versus control subjects. Results Klotho and phosphorus CSF levels were lower in narcoleptic patients than in control (908.18 ± 405.51 versus 1265.78 ± 523.26 pg/ml; p = 0.004 and 1.34 ± 0.25 versus 1.58 ± 0.23 mg/dl; p = 0.001, respectively). We found higher FGF-23 levels in narcoleptic patients (5.51 versus 4.00 pg/mL; p = 0.001). Klotho and phosphorus CSF levels were lower in both HCRT- and HCRT+ than controls. Moreover, there were higher FGF-23 levels in both HCRT-/HCRT+ groups versus controls. However, we did not find differences comparing HCRT- and HCRT+ groups, analyzing CSF klotho, FGF-23 or phosphorus levels. Conclusions Patients with narcolepsy have decreased CSF concentration of klotho and increased CSF levels of FGF-23. These findings may play a role in understanding the pathogenesis of narcolepsy.

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.

Entrapments of the intrapelvic portions of the lumbosacral plexus are an important extraspinal cause of sciatica and pudendal neuralgia. They can be treated using Laparoscopic Neuronavigation (LANN), a minimally invasive technique that has set the foundations of an emerging field in Medicine—Neuropelveology. This retrospective-prospective study analyzes the outcomes of 63 patients treated with the LANN technique over a 10 year time period. One year after surgery, 78.3% of patients reported clinically relevant pain reduction, defined as ≥ 50% reduction in Numeric Rating Scale (NRS) score; these results were maintained for a mean follow up of 3.2 years. Preoperative chronic opioid use (≥ 4 months of ≥ 10 mg morphine equivalents/day) was a predictor of poor surgical outcome—clinically relevant pain reduction was observed in only 30.8% in this group of patients, compared to 91.5% in patients not regularly taking opioids preoperatively (p

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. RESUMO Embora o diagnóstico da EM tenha se modificado na última década, ainda tem como requisito básico a demonstração da disseminação no tempo e no espaço, através do quadro clínico e do exame de ressonância magnética. A síntese intratecal de imunoglobulina pode ser um marcador inespecífico e não há biomarcadores plasmáticos que sejam úteis no diagnóstico da EM, impondo desafios à sua detecção precoce. Métodos Realizamos uma análise lipidômica preliminar por espectrometria de massas, não direcionada, qualitativa, comparando amostras de LCR e plasma de pacientes com EM, outras doenças neurológicas inflamatórias e hipertensão intracraniana idiopática (HII). Resultados A identificação lipídica revelou que os ácidos graxos e esfingolipídios foram as classes mais abundantes de lipídios no LCR e que glicerolipídios e ácidos graxos foram a principal classe de lipídios no plasma de pacientes com EM. A AUC foi de 0,995 (0,912–1) e 0,78 (0,583–0,917), respectivamente. O teste de permutação indicou que essa combinação de íons foi útil para distinguir a EM de outras doenças inflamatórias (p < 0,001 e 0,055, respectivamente). Conclusão Este estudo sugere que o líquido cefalorraquidiano (LCR) e o plasma de pacientes com EM possuem uma assinatura lipídica única, pode ser útil como um biomarcador diagnóstico.

Introduction: Infiltration of the central nervous system 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. Objective: To calculate the diagnostic performance of flow cytometry using a cell stabilizer for sample preservation compared to cytomorphology in the detection of central nervous system infiltration by lymphoid and hematologic neoplasms. Methods: Cell samples from all consecutive patients with suspected infiltration by hematological malignancies evaluated between January 2014 and December 2016 were included. Cases were analyzed by flow cytometry using a cell preservation medium and cytomorphology. Sensitivity and specificity were calculated. Results: From 414 CSF samples, 72 had a phenotype compatible with characteristics of infiltration by hematological disease, whereas cytology was positive for 35 cases. Flow cytometry showed higher sensitivity and specificity when compared to cytomorphology, particularly in cases with cellularity under 5 leukocytes/mm3. Conclusion: We demonstrated that collecting cerebrospinal fluid 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 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. RESUMO A análise do líquido cefalorraquidiano tem sido empregada para avaliação diagnóstica da esclerose múltipla e a exclusão dos diagnósticos diferenciais. Os achados clássicos refletem a natureza inflamatória da doença, incluindo discreta pleocitose, leve hiperproteinorraquia, aumento da síntese intratecal de imunoglobulina G e, mais tipicamente, a presença de bandas oligoclonais. Nos últimos anos, surgiram novos biomarcadores para esclerose múltipla, e esta busca por marcadores reflete a necessidade de melhor avaliar a atividade e a progressão da doença, bem como a eficácia terapêutica. Uma avaliação mais refinada da atividade da doença e da resposta aos medicamentos pode contribuir para melhores decisões terapêuticas, particularmente no que se refere à troca de medicação. Isto é muito importante nos dias de hoje, quando surgem novas opções medicamentosas. Neste artigo de revisão, avaliamos criticamente a literatura atual referente aos novos marcadores liquóricos na esclerose múltipla. A mensuração destes marcadores, como a quimiocina CXCL13, fetuína A e, principalmente, o neurofilamento de cadeia leve, demonstrou resultados promissores na avaliação da doença, provendo informações que, em conjunto com dados clínicos e de neuroimagem, podem contribuir para melhores decisões terapêuticas.

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.