Analysis on Components Absorbed into Blood and Cerebrospinal Fluid of Schisandrae Chinensis Fructus Based on Sequential Metabolism / 中国实验方剂学杂志

ObjectiveTo identify the prototypical components and metabolites absorbed into blood and cerebrospinal fluid of Schisandrae Chinensis Fructus（SCF） based on sequential metabolism combined with liquid chromatography-mass spectrometry. MethodBlood and cerebrospinal fluid samples of integrated metabolism， intestinal metabolism and hepatic metabolism were collected from male SD rats after gavage and in situ intestinal perfusion administration， and ultra-performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry（UPLC Q-Exactive Orbitrap MS） was used to analyze and compare the differences in the spectra of SCF extract， blank plasma， administered plasma， blank cerebrospinal fluid and administered cerebrospinal fluid with ACQUITY UPLC BEH Shield RP18 column（2.1 mm×100 mm， 1.7 µm）， the mobile phase was acetonitrile（A）-0.1% formic acid aqueous solution（B） for gradient elution（0-7 min， 95%B； 7-12 min， 95%-35%B； 12-17 min， 35%-15%B； 17-20 min， 15%-12%B； 20-22 min， 12%-5%B； 22-23 min， 5%B； 23-25 min， 5%-95%B； 25-28 min， 95%B）. And heated electrospray ionization（HESI） was used with positive and negative ion modes， the scanning range was m/z 100-1 500. The prototypical constituents and their metabolites absorbed into blood and cerebrospinal fluid of SCF were identified according to the retention time， characteristic fragments， molecular formulae and the information of reference substances. ResultA total of 42 chemical components were identified in the extract of SCF， including lignans， flavonoids， amino acids， tannins， and others， of which lignans were the main ones. A total of 27 prototypical components and 14 metabolites were identified in plasma samples from different sites. A total of 15 prototypical components and 9 metabolites were identified in cerebrospinal fluid. The main metabolic reactions involved in the formation of metabolites were mainly demethylation， methylation， demethoxylation and hydroxylation. ConclusionThrough the systematic identification of the prototypical components and metabolites of SCF in rats， it provides data support for further better exploring the material basis of SCF in the treatment of central nervous system diseases.

Review of dengue, zika and chikungunya infections in nervous system in endemic areas / Revisão da infecção por dengue, zika e chikungunya no sistema nervoso em áreas endêmicas

Abstract Dengue, zika, and chikungunya are arboviruses of great epidemiological relevance worldwide. The emergence and re-emergence of viral infections transmitted by mosquitoes constitute a serious human public health problem. The neurological manifestations caused by these viruses have a high potential for death or sequelae. The complications that occur in the nervous system associated with arboviruses can be a challenge for diagnosis and treatment. In endemic areas, suspected cases should include acute encephalitis, myelitis, encephalomyelitis, polyradiculoneuritis, and/or other syndromes of the central or peripheral nervous system, in the absence of a known explanation. The confirmation diagnosis is based on viral (isolation or RT-PCR) or antigens detection in tissues, blood, cerebrospinal fluid, or other body fluids, increase in IgG antibody titers between paired serum samples, specific IgM antibody in cerebrospinal fluid and serological conversion to IgM between paired serum samples (non-reactive in the acute phase and reactive in the convalescent). The cerebrospinal fluid examination can demonstrate: 1. etiological agent; 2. inflammatory reaction or protein-cytological dissociation depending on the neurological condition; 3. specific IgM, 4. intrathecal synthesis of specific IgG (dengue and chikungunya); 5. exclusion of other infectious agents. The treatment of neurological complications aims to improve the symptoms, while the vaccine represents the great hope for the control and prevention of neuroinvasive arboviruses. This narrative review summarizes the updated epidemiology, general features, neuropathogenesis, and neurological manifestations associated with dengue, zika, and chikungunya infection.

Resumo Dengue, zika e chikungunya são arboviroses de grande relevância epidemiológica em todo o mundo. A emergência e reemergência dessas infecções virais transmitidas por mosquitos constituem um grave problema de saúde pública humana. As manifestações neurológicas causadas por esses vírus têm alto potencial de morte ou sequelas. As complicações que ocorrem no sistema nervoso associadas às arboviroses podem representar um desafio diagnóstico e de tratamento. Em áreas endêmicas, casos suspeitos devem incluir encefalite, mielite, encefalomielite, polirradiculoneurite e/ou outras síndromes do sistema nervoso central ou periférico, na ausência de explicação conhecida. Caso confirmado de arbovirose neuroinvasivo é baseado na detecção viral (isolamento ou RT-PCR) ou de antígenos em tecidos, sangue, líquido cefalorraquidiano ou outros fluidos corporais, aumento dos títulos de anticorpos IgG entre amostras de soro pareadas, anticorpo IgM específico no líquido cefalorraquidiano e conversão sorológica para IgM entre amostras de soro pareadas. O exame do líquido cefalorraquidiano pode demonstrar: 1. agente etiológico; 2. reação inflamatória ou dissociação proteico-citológica, dependendo do quadro neurológico; 3. valor absoluto de IgM específica; 4. síntese intratecal de anticorpos IgG específicos (dengue e chikungunya); 5. exclusão de outros agentes infecciosos. O tratamento das complicações neurológicas visa melhorar os sintomas, enquanto a vacina representa a grande esperança para o controle e a prevenção das arboviroses neuroinvasivas. Esta revisão narrativa resume a atualização da epidemiologia, características gerais, neuropatogênese e manifestações neurológicas associadas à infecção pelos vírus da dengue, zika e chikungunya.

Optic nerve sheath fenestration: A second lease at sight

Purpose: To study the safety and efficacy of optic nerve sheath fenestration surgery in patients with optic disc edema due to different etiologies. Methods: Records of 18 eyes of 15 patients who underwent optic nerve sheath fenestration for vision threatening optic disc edema were reviewed retrospectively, and results were analyzed. Improvement of visual acuity was the main measure of outcome. Improved visual fields, resolution of optic disc edema, diplopia, and headache were other benefits that were observed. Results: Fifteen patients between 13 and 54 years of age were included in the study. Three patients underwent successive bilateral surgery. Idiopathic intracranial hypertension was the most common cause for optic disc edema and was found in 80% of the patients. Mean preoperative logMAR acuity was ?1.9789 ± 1.46270, which improved to ?0.9022 ± 1.23181 (p < 0.005) in the operated eye, and mean logMAR acuity of contralateral eye improved from ?1.3378 ± 1.50107 to ?1.0667 ± 1.33813 (p < 0.05). Conclusion: Early optic nerve sheath fenestration is an effective modality for treating optic disc edema due to a wide myriad of causes and helps resolve the associated symptoms.

Sistema glinfático: aspectos anatómicos, fisiológicos e implicaciones clínicas

Introducción: El sistema glinfático comprende el conjunto de rutas perivasculares tanto arteriales como venosas que se encuentran en estrecha asociación con células astrogliales y que permiten la interacción entre el líquido cefalorraquídeo (LCR) y el líquido intersticial cerebral (LIC), para llevar a cabo procesos como la depuración de los metabolitos de desecho celular, o la distribución de nutrientes, así como contribuir al metabolismo cerebral local, la transmisión de volumen y la señalización paracrina cerebral. Contenidos: Este artículo busca profundizar en los conceptos anatómicos y fisiológicos, hasta el momento descritos, sobre este sistema macroscópico de transporte. Se realiza una búsqueda bibliográfica de revisiones y estudios experimentales sobre la anatomía, la fisiología y las implicaciones fisiopatológicas del sistema glinfático. Conclusiones: La identificación anatómica y funcional del sistema glinfático ha ampliado el conocimiento sobre la regulación del metabolismo cerebral en cuanto a distribución de nutrientes y cascadas de señalización celular. Al establecer una interacción entre el espacio subaracnoideo subyacente y el espacio intersticial cerebral, el sistema glinfático surge como uno de los mecanismos protagonistas de la homeostasis cerebral. La disfunción de esta vía hace parte de los mecanismos fisiopatológicos de múltiples trastornos neurológicos, ya sea por la acumulación de macromoléculas, como ocurre en la enfermedad de Alzheimer, o por la reducción del drenaje de sustancias químicas y citocinas proinflamatorias en patologías como la migraña o el trauma craneoencefálico.

Introduction: The glympathic system comprises the set of perivascular routes, arterials or venous, that are found in close relationship with astroglial cells and allow interaction between the cerebrospinal fluid (CSF) and the interstitial brain fluid (ISF), to carry processes like cell-wasting metabolites depuration, nutrients distribution, as well as make a contribution in the local brain metabolism, volumen transmition and brain paracrine signaling. Contents: This article seeks to deepen in the anatomical and physiological concepts, so far described, about this macroscopic transport system. A bibliographic search of reviews and experimental studies on the anatomy, physiology and pathophysiological implications of the glymphatic system is carried out. Conclusions: Anatomical and functional identification of glympathic system has broaden the knowledge about regulation of brain metabolism on the nutrients distribution and cell signaling cascades. When setting an interaction between the subarachnoid space and the brain interstitial space, the glymphatic system arise as one of the leading mechanisms of brain homeostasis. Disfunction of this pathway makes part of the patophysiological mechanisms of multiple neurological disease, either be by collection of macromolecules as in Alzheimer's disease, or by the reduction of inflammatory cytokines and chemical substances drainage as in migraine or traumatic brain injury (TBI).

Potenciales biomarcadores moleculares de infiltración a sistema nervioso central en leucemia linfoblástica aguda / Central nervous system potential molecular biomarkers in acute lymphoblastic leukemia

Resumen La leucemia linfoblástica aguda es el tipo de leucemia más frecuente en niños entre los 2 y 3 años. A nivel internacional la población hispana es reportada como la más prevalente. En México se carece de información reciente, sin embargo, se conoce que es uno de los cánceres más frecuentes en niños. La infiltración de células linfoblásticas a sistema nervioso central es una complicación de pronóstico ominoso que puede presentarse en los pacientes con leucemia linfoblástica aguda, actualmente el diagnóstico se establece mediante citología de líquido cefalorraquídeo, sin embargo, es una prueba operador dependiente y que es afectada por el número de punciones realizadas en la toma de líquido cefalorraquídeo, con potencial contaminación con sangre. En distintos estudios se han caracterizado 6 genes que presentan una sobreexpresión en líquido cefalorraquídeo cuando se presenta dicha infiltración, en esta revisión analizamos estos nuevos marcadores y su potencial como herramientas de diagnóstico oportuno.

Abstract Acute lymphoblastic leukemia is the most common type of leukemia in children between 2 and 3 years of age. Internationally, hispanic population is reported as the most prevalent. In Mexico there is few recent information, however, it is known that it is one of the most frequent cancers in children. Infiltration of lymphoblastic cells into the central nervous system is an ominous prognostic complication that can occur in patients with acute lymphoblastic leukemia. Currently, diagnosis is established by cerebrospinal fluid cytology, however, this technique is affected by the number of punctions done while obtaining the fluid. In several research studies, 6 genes have been identified to be overexpressed in cerebrospinal fluid when infiltration occurs. In this review we analyzed these new molecular biomarkers and their potential as tools for timely diagnosis.

Impact of Reconstructing Intercostal Artery on Spinal Cord Circulation During Open Surgery for Thoracoabdominal Aortic Aneurysm

ABSTRACT Introduction: We evaluated the outcomes of the selective intercostal artery reconstruction for preventing spinal cord injury during thoracoabdominal aortic aneurysm repair. Methods: We retrospectively assessed 84 consecutive patients who underwent thoracoabdominal aortic aneurysm repairs between 2004 and 2016. The mean age of the patients was 57.3 years. We performed preoperative multidetector computed tomography in 74 patients (88.0%) to identify the Adamkiewicz artery. Spinal cord injury preventive measures included motor evoked potential monitoring, hypothermia induction, Adamkiewicz artery or other intercostal artery reconstruction, and cerebrospinal fluid drainage. Results: The hospital death rate was 5.9%, and paraplegia occurred in four patients (4.7%). The Adamkiewicz artery or other intercostal arteries were reconstructed selectively in 46 patients (54.7%). Of these patients, 41 underwent postoperative multidetector computed tomography, which revealed occlusion of the reconstructed grafts in 23 patients (56.0%). There was no paraplegia in the patients who underwent reconstruction of the Adamkiewicz artery, which was patent on postoperative multidetector computed tomography. Univariate analysis showed no significant effect of various risk factors on the development of spinal cord injury. Conclusion: Outcome of open surgery for thoracoabdominal aortic aneurysm in our institution regarding spinal cord injury was satisfactory. The benefits of Adamkiewicz artery reconstruction remain inconclusive, and further larger studies are required to identify its validation for spinal cord protection in thoracoabdominal aortic aneurysm repair.

Use of cerebrospinal fluid CXCL13 concentration for diagnosis and monitoring of neurosyphilis: a three-case report

Introduction: Previous retrospective studies have demonstrated that the concentration of chemokine ligand CXCL13 in cerebrospinal fluid (CSF-CXCL13) is a promising biomarker in the diagnosis of neurosyphilis and, additionally, in the monitoring of therapeutic efficacy. Objective: To describe three cases of patients with neurosyphilis (NS) treated at Hospital Universitário Gaffrée e Guinle, in Rio de Janeiro, Brazil, with suspected active syphilis with neurological symptoms. Case report: Three patients from Rio de Janeiro, Brazil, were investigated for symptomatic NS. The concentration of CSF-CXCL13 was prospectively performed by enzyme-linked immunosorbent assay (ELISA) in all participants at baseline and in follow-up visits at 3 months after therapy. CSF-CXCL13 concentrations were significantly higher in all three patients with established NS. The CSF-CXCL13 concentrations decreased after 3 months of therapy compared to baseline in all cases reported. The added high concentration of CSF-CXCL13 plus CSF-TPHA reactivity above 1:40 titer agreed with the diagnosis of NS in 100% of the cases. Conclusion: In this case series, we present three cases of NS diagnosed using CXCL13 in CSF as a complementary test. These case series suggest that the clinical use of CSF-CXCL13 is useful as a supplementary biomarker for NS and for monitoring the effectiveness of NS therapy, especially in patients with nonreactive CSF-VDRL, excluding other neurologic diseases

Cerebrospinal fluid evaluation as a diagnosis and prognosis tool: a bibliometric analysis of the 100 most cited articles / Avaliação do líquido cefalorraquidiano enquanto ferramenta diagnóstica e prognóstica: uma análise bibliométrica dos 100 artigos mais citados / Evaluación del líquido cefalorraquídeo como herramienta de diagnóstico y pronóstico: un análisis bibliométrico de los 100 artículos más citados

Introduction: Cerebrospinal fluid (CSF) analysis is critical in the diagnosis, prognosis, and treatment of a wide range of diseases, including multiple sclerosis, encephalitis, meningitis, brain tumors, Creutzfeldt-Jakob disease, Alzheimer's disease, and other neurodegenerative conditions. Objective: Bibliometric analysis of the 100 most cited articles to obtain deeper insights into the status of research in this sector, in order to provide support for evidence-based medicine (EBM). Methodology: The main collection of the Web of Science was used to collect relevant studies on the topic, and the VOSviewer software was employed to build bibliometric networks. The examination did not include materials from editorials, books, patents, or research with unspecified designs. The articles chosen are in the time range from 1991 to 2020. Results: It was noted that most of the articles were human observational studies focusing on the diagnosis of neurodegenerative diseases, specifically Alzheimer's, which were published in neurology and/or Alzheimer's-related journals, mainly in the United States of America. We discovered forward-looking research hotspots and trends in this domain, which can serve as an important guide to neurological research, generating subsidies for medical decision- making. Conclusion: The number of primary articles on the subject points to the need for further future research on CSF associated, mainly, with other neurodegenerative diseases, in addition to Alzheimer's, sustaining the diagnostic efficacy and EBM.

Introdução: A análise do líquido cefalorraquidiano (LCR) é fundamental no diagnóstico, prognóstico e tratamento de uma ampla gama de doenças, incluindo esclerose múltipla, encefalite, meningite, tumores cerebrais, doença de Creutzfeldt-Jakob, doença de Alzheimer e outras condições neurodegenerativas. Objetivo: Análise bibliométrica dos 100 artigos mais citados para obter insights mais aprofundados sobre o status da pesquisa nesse setor, a fim de fornecer subsídios para a medicina baseada em evidências (MBE). Metodologia: O acervo principal da Web of Science foi utilizado para coletar estudos relevantes sobre o tema, e o software VOSviewer foi empregado para construir redes bibliométricas. O exame não incluiu materiais de editoriais, livros, patentes ou pesquisas com desenhos não especificados. Os artigos escolhidos estão no intervalo de tempo de 1991 a 2020. Resultados: Observou-se que a maioria dos artigos eram estudos observacionais humanos com foco no diagnóstico de doenças neurodegenerativas, especificamente Alzheimer, que foram publicados em revistas de neurologia e/ou relacionadas ao Alzheimer, principalmente nos Estados Unidos da América. Descobrimos focos de pesquisa prospectivos e tendências nesse domínio, que podem servir como um importante guia para a pesquisa neurológica, gerando subsídios para a tomada de decisões médicas. Conclusão: O número de artigos primários sobre o tema aponta para a necessidade de novas pesquisas futuras sobre LCR associado, principalmente, a outras doenças neurodegenerativas, além da doença de Alzheimer, sustentando a eficácia diagnóstica e a BEM.

Introducción: El análisis del líquido cefalorraquídeo (LCR) es crítico en el diagnóstico, pronóstico y tratamiento de una amplia gama de enfermedades, incluyendo esclerosis múltiple, encefalitis, meningitis, tumores cerebrales, enfermedad de Creutzfeldt-Jakob, enfermedad de Alzheimer y otras afecciones neurodegenerativas. Objetivo: Análisis bibliométrico de los 100 artículos más citados para profundizar en el estado de la investigación en este sector, con el fin de dar soporte a la medicina basada en la evidencia (MBE). Metodología: Se utilizó la colección principal de la Web of Science para recopilar estudios relevantes sobre el tema, y se empleó el software VOSviewer para construir redes bibliométricas. El examen no incluyó materiales de editoriales, libros, patentes o investigaciones con diseños no especificados. Los artículos elegidos están en el rango de tiempo de 1991 a 2020. Resultados: Se observó que la mayoría de los artículos eran estudios observacionales en humanos centrados en el diagnóstico de enfermedades neurodegenerativas, específicamente Alzheimer, que fueron publicados en revistas de neurología y/o relacionadas con el Alzheimer, principalmente en los Estados Unidos de América. Descubrimos puntos calientes de investigación con visión de futuro y tendencias en este dominio, que pueden servir como una guía importante para la investigación neurológica, generando subsidios para la toma de decisiones médicas. Conclusión: El número de artículos primarios sobre el tema apunta a la necesidad de futuras investigaciones sobre el LCR asociadas, principalmente, con otras enfermedades neurodegenerativas, además del Alzheimer, manteniendo la eficacia diagnóstica y la MBE.

Cerebrospinal fluid levels of hypothalamic-pituitary-adrenal axis hormones in MCI and dementia due to Alzheimer's disease: a systematic review / Níveis dos hormônios do eixo hipotálamo-pituitária-adrenal no líquido cefalorraquidiano de pacientes com CCL e demência devido à doença de Alzheimer: uma revisão sistemática

ABSTRACT Underlying the neuropsychological manifestations of Alzheimer's disease (AD), hypothalamic-pituitary-adrenal (HPA) axis dysregulation and subsequent hypercortisolemia have been proposed as major mechanisms driving AD progression from mild cognitive impairment (MCI) to the onset of dementia. Nonetheless, changes in cerebrospinal fluid (CSF) levels of HPA axis hormones remain controversial despite their potential in AD diagnosis and prognosis testing. Objective: This study aimed to review the evidence of the variation in CSF levels of CRH, ACTH, and cortisol in subjects with mild cognitive impairment (MCI) and AD compared with subjects without cognitive disorders. Methods: A systematic review was conducted in MEDLINE, EMBASE, and Web of Science databases on July 5, 2022. Results: Seventeen observational studies were included. The results from the compiled investigations showed that individuals with AD exhibit a significant elevation of CSF cortisol levels which appear to correlate with the presence of the ApoE-ε4 allele, being higher in those homozygous for this allele. The variation of CSF CRH and ACTH levels in AD, on the other hand, is still inconclusive. Moreover, most studies found no significant difference in CSF cortisol levels in individuals with MCI compared to healthy subjects and patients with AD. Conclusion: The findings gathered in this review disclose a significant elevation of CSF cortisol levels in AD. Future investigations are warranted to elucidate the potential use of CSF cortisol as a biomarker in AD-associated dementia.

RESUMO Subjacentes às manifestações neuropsicológicas da doença de Alzheimer (DA), a desregulação do eixo hipotálamo-pituitária-adrenal (HPA) e a subsequente hipercortisolemia foram propostas como mecanismos principais que conduzem a progressão da DA desde o comprometimento cognitivo leve (CCL) até o início da demência. No entanto, as alterações nos níveis do líquido cefalorraquidiano (LCR) dos hormônios do eixo HPA permanecem controversas, apesar de seu potencial no diagnóstico da DA e nos testes de prognóstico. Objetivo: Este estudo teve como objetivo revisar as evidências da variação nos níveis de CRH, ACTH e cortisol em indivíduos com comprometimento cognitivo leve (CCL) e DA em comparação com indivíduos sem distúrbios cognitivos. Métodos: Uma revisão sistemática foi realizada nas bases de dados MEDLINE, EMBASE e Web of Science em 5 de julho de 2022. Resultados: Dezessete estudos observacionais foram incluídos. Os resultados compilados mostraram que os indivíduos com DA apresentam uma elevação significativa dos níveis de cortisol no LCR que parecem correlacionar-se com a presença do alelo ApoE-ε4, sendo maior nos homozigotos para este alelo. A variação dos níveis de CRH e ACTH no LCR na DA, por outro lado, ainda é inconclusiva. Além disso, a maioria dos estudos não encontrou diferença significativa nos níveis de cortisol no LCR em indivíduos com CCL em comparação com indivíduos saudáveis e pacientes com DA. Conclusão: Os resultados reunidos nesta revisão revelaram uma elevação significativa dos níveis de cortisol no LCR na DA. Investigações futuras são necessárias para elucidar o uso potencial do cortisol no LCR como biomarcador na demência associada à DA.

Síndrome De Hipotensión Endocraneana Espontánea: Reporte De Un Caso Clínico / Spontaneous Intracranial Hypotension Syndrome: Clinic Case Report

La hipotensión intracraneal espontánea (SIH) es una patología con una incidencia anual aproximada de 5 por cada 100.000 personas al año, caracterizada clásicamente por cefalea ortostática comúnmente secundaria a una fuga espontánea de líquido cefalorraquídeo (LCR), pudiendo existir a su vez una amplia gama de síntomas asociados. El diagnóstico se centra en la clínica y en hallazgos típicos en la resonancia nuclear magnética (RM), sin embargo, según diversos estudios, puede corresponder a una patología subdiagnosticada por la dificultad que ha existido en definir criterios diagnósticos universales y un manejo terapéutico estandarizado, el cual varía inicialmente entre manejo médico conservador y/o parches de sangre epidural (PHE). Reportamos el caso de una paciente femenina de 51 años quien fue atendida en el Hospital Herminda Martin de Chillán donde se realizó el diagnóstico y tratamiento sintomático con PHE.

Spontaneous intracranial hypotension (SIH) is a pathology with an annual incidence of approximately 5 per 100,000 people per year, classically characterized by orthostatic headache commonly secondary to a spontaneous cerebrospinal fluid (CSF) leak, and there may also be a wide range of of associated symptoms. The diagnosis is centered on the clinic and on typical findings in magnetic resonance imaging (MRI), however, according to various studies, it may correspond to an underdiagnosed pathology due to the difficulty that has existed in defining universal diagnostic criteria and standardized therapeutic management. which initially varies between conservative medical management and/or epidural blood patches (PHE). We report the case of a 51-year-old female patient who was treated at the Herminda Martin de Chillán Hospital where the diagnosis and symptomatic treatment with PHE were made.

Comparative analysis between cytomorphology and flow cytometry methods in central nervous system infiltration assessment in oncohematological patients

ABSTRACT Introduction Oncohematological patients require the evaluation for possible infiltration of the central nervous system (CNS) by neoplastic cells at diagnosis and/or during the monitoring of the chemotherapeutic treatment. Morphological analysis using conventional microscopy is considered the method of choice to evaluate the cerebrospinal fluid (CSF) samples, despite technical limitations. Objective This study aimed to compare the performance of the cytomorphology and flow cytometric immunophenotyping (FC) in the detection of CNS infiltration. Method We evaluated 520 CSF samples collected from 287 oncohematological patients for whom the detection of neoplastic cells was simultaneously requested by cytomorphology and FC. Results Laboratory analyses revealed 435/520 (83.7%) conclusive results by the two methods evaluated, among which 385 (88.5%) were concordant. Discordance between the methods was observed in 50/435 (11.5%) samples, 45 (90%) being positive by FC. Furthermore, the FC defined the results in 69/72 (95.8%) inconclusive samples by cytomorphology. The positivity of FC was particularly higher among hypocellular samples. Among 431 samples with a cell count of < 5/μL, the FC identified neoplastic cells in 75 (17.4%), while the cytomorphology reported positive results in 26 (6%). Among the samples that presented adequate cell recovery for evaluation by both methods (506/520), the comparative analysis between FC and cytomorphology revealed a Kappa coefficient of 0.45 (CI: 0.37-0.52), interpreted as a moderate agreement. Conclusion The data showed that the CSF analysis by FC helps in the definition of CNS infiltration by neoplastic cells, particularly in the cases with dubious morphological analysis or in the evaluation of samples with low cellularity.

Apport de l'imagerie dans les brèches ostéoméningées de l'étage antérieur de la base du crâne / Role of imaging in the osteo-dural defects of the anterior base of the skull

Décrire les caractéristiques radiologiques de la brèche ostéo-méningée (BOM) de l'étage antérieur de la base du crâne. Méthodes: Etude rétrospective, descriptive, monocentrique, colligeant les patients hospitalisés pour prise en charge d'une brèche ostéoméningée (BOM) et explorés par le couple TDM/IRM, du 1er janvier 2012 au 31 Décembre 2021. Résultats: Ont été retenu 23 patients avec un âge moyen de 48 ans et un sex ratio de 0,3. Des antécédents de chirurgie nasosinusienne ou de neurochirurgie ont été notés chez deux patients (9 %). Treize patients (57 %) étaient victimes de traumatisme crânien. Une rhinoliquorrhée était retrouvée dans 21 cas (persistante dans trois cas (12%) et intermittente dans 18 cas (76%)). La découverte de la BOM a été faite suite à une méningite dans quatre cas. Le dosage de la bêta trace a confirmé la présence de LCR chez deux patients. La TDM a confirmé le diagnostic chez 12 patients dont deux patients qui ne présentaient pas de rhinoliquorrhée à l'examen clinique. Elle a aussi permis d'établir le bilan topographique dans ces cas. Elle a suspecté une BOM dans 9 cas et était négative dans deux cas. L'IRM a confirmé le diagnostic dans tous les cas et a permis de: localiser le siège de la fuite de LCR dans les brèches multiples, confirmer le diagnostic deméningoencéphalocèle (trois cas) et objectiver des signes indirects d'hypertension intra-crânienne (HTIC) (quatre cas). Conclusion: L'imagerie en coupes permet de localiser la BOM mais nécessite souvent, une approche par étapes et son interprétation exige une connaissance approfondie de l'anatomie normale et des variantes de la base du crâne. Mots-clés: Liquorrhée, Brèche Ostéoméningée, Chirurgie, TDM, IRM

Establishing and evaluating a robust method based on LC-MS/MS for simultaneous determination of Aβ1-42,Aβ1-40 and A β1-38 in cerebrospinal fluid / 中华检验医学杂志

Objective:To establish and validate an LC-MS/MS method for simultaneous determination of Aβ 1-42, Aβ 1-40, and Aβ 1-38 in cerebrospinal fluid. Additionally, the consistency between this method and three mainstream detection methods was evaluated.Methods:This study involved method establishment, validation, and consistency evaluation. The N15 labeled β-amyloid protein was used as the internal standard. Extraction was performed using Waters MCX 96-wells solid phase extraction plate, and the eluent was collected to QuanRecovery MaxPeak 700 μl plate. At the positive ion mode, the multi-reaction ion monitoring mode based on electric spray ionization is chosen for the determination of CSF Aβ 1-42, Aβ 1-40, and Aβ 1-38. Referring to the CLSI C62-A and EP-15A3 guidelines, the method is evaluated and verified, including quantitation of limit (LOQ), linearity, recovery, precision, and accuracy. In addition, a total of 57 clinical residual CSF samples were collected and the concentrations of Aβ 1-42 and Aβ 1-40 were determined based on manual INNOTEST ELISA assay and Lumipulse G and Roche Elecsys fully automated biochemical analyzers. The comparison analysis and deviation evaluation were conducted by passing-bablok and Bland Altman methods.Results:The analysis time of this method is 8 min, and the LOQ of Aβ 1-42, Aβ1-40 and Aβ1-38 is 0.1 ng/ml, 0.5 ng/ml, and 0.1 ng/ml, respectively, and the linear range can meet the needs of clinical detection. Respectively, the recovery is 86.2%-93.8%, 100.9%-103.9% and 103.3%-107.1%; the total imprecision is 4.7%-7.4%, 3.5%-4.6% and 5.2%-10.9%. The measured values of Aβ 1-42 certified reference materials are all within the allowable uncertainty requirements. Moreover, the carryover rate of three analytes was all≤0.11%. In addition, the correlations of Aβ 1-42 and Aβ1-40 in CSF between this LC-MS/MS method and the INNOTEST ELISA method, Lumipulse G and Roche Elecsys fully automated biochemical analyzers were all deemed good, with correlation coefficient (r) ranging from 0.920 to 0.970. However, the measured values between the four methods were remarkably different.Conclusion:We established and validated a robust method based on LC-MS/MS technology for simultaneous determination of Aβ 1-42, Aβ 1-40, and Aβ 1-38 in CSF. The method is accurate, simple, and suitable for clinical measurements. However, despite good correlations, there were substantial differences in the measurement results of Aβ 1-42 and Aβ 1-40 among different analytical platforms, indicating the need for further promotion of harmonization and standardization processes for AD classic biomarkers.

Spontaneous intracranial hypotension: analysis of 118 patients ' clinical characteristics / 中华神经科杂志

Objective:To summarize the clinical features, radiological characteristics, therapy, and outcome of patients with spontaneous intracranial hypotension (SIH).Methods:The general information, clinical manifestations, auxiliary examinations, treatment, and outcomes in consecutive patients of SIH hospitalized in the Xuanwu Hospital, Capital Medical University from November 2018 to October 2022 were analyzed.Results:A total of 118 patients with a female-to-male ratio of 5∶4 were included and the ages were 17.00-71.00[39.00(34.00,46.75)]years with a preponderance in the age of 30-49 years. Almost all patients had orthostatic headaches (117/118, 99.2%), accompanied by nausea (90/118, 76.3%), vomiting (70/118, 59.3%), neck stiffness (88/118, 74.6%), tinnitus (57/118, 48.3%), and ear fullness (57/118, 48.3%). Brain magnetic resonance imaging (MRI) showed dural enhancement (97/113, 85.8%), enlarged venous sinus (88/113, 77.9%), subdural fluid collection (46/113, 40.7%), decreased suprasellar cistern (86/113, 76.1%), effacement of the prepontine cistern (86/113, 76.1%), diminished mamillopontine distance (80/113, 70.8%). The cerebrospinal fluid (CSF) leaks were detected in 90.7% (107/118) of the patients by magnetic resonance myelography but 54.3% (25/46) and 52.6% (20/38) by CT myelography and magnetic resonance myelography with gadolinium. Lumber puncture found CSF pressure<60 mmH 2O (1 mmH 2O=0.009 8 kPa) in 18.4% (19/103) of patients, increased CSF red blood cell counts in 50.6% (44/87) of patients, CSF pleocytosis in 44.8% (39/87) of patients, increased CSF protein concentrations in 57.5% (50/87) of patients. The headache completely disappeared after conservative treatment in 24.6% (31/118) of patients and after a single targeted epidural blood patch in 89.7% (78/87) of patients. A rebound headache after epidural blood patch treatment occurred in 66.0% (58/87) of patients. Conclusions:The patients with SIH almost manifested with orthostatic headache, and brain MRI and magnetic resonance myelography were suggested in those patients instead of CSF pressure by lumber puncture. Targeted epidural blood patch was effective and safe in SIH patients.

The key points in diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy / 中华神经科杂志

The diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy relies on clinical features, demyelinating changes on motor and sensory nerve conduction studies, elevated cerebrospinal fluid protein, peripheral nerve image, nerve pathology, and response to immune therapy. Each diagnostic proof should be interpreted in light of clinical background and other findings, to avoid misdiagnosis or overdiagnosis, treatment delay or unnecessary treatment with immunotherapy.

Diagnosis of a case of leptomeningeal metastasis from endometrial carcinoma by next-generation sequencing and cerebrospinal fluid cytology / 中华神经科杂志

Endometrial carcinoma is one of common malignant tumors in female reproductive system, but it is extremely rare in leptomeningeal metastasis. The clinical manifestations and signs of meningeal carcinomatosis are complex and not specific. It is difficult to get a precise diagnosis early, and it has high rate of misdiagnosis and missed diagnosis. Accurate diagnosis and treatment of a case of leptomeningeal metastasis from endometrial carcinoma by next-generation sequencing and cerebrospinal fluid cytology are reported. The patient is an elderly female with a history of endometrial cancer. The main manifestations were fever, headache and dizziness; cerebrospinal fluid cytology showed tumor cells; AKT1 gene and TP53 gene were detected in endometrial carcinoma tissue, plasma and cerebrospinal fluid by next-generation sequencing. After treatment with intrathecal chemotherapy, immunotherapy combined with anti angiogenesis, the patient′s condition still progressed gradually and died finally. The purpose of this case report is to raise clinical awareness of recognition and treatment in early meningeal metastasis of endometrial carcinoma.

Detection of meningeal carcinomatosis by metagenomic next-generation sequencing and copy number variation analysis of cerebrospinal fluid / 中华神经科杂志

Objective:To evaluate the significance of copy number variation (CNV) and metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid (CSF) in the diagnosis of meningeal carcinomatosis (MC).Methods:Ten patients with MC diagnosed in the Department of Neurology of Peking Union Medical College Hospital from March 2022 to June 2022 were consecutively enrolled in this study. The patients were diagnosed according to the criteria of the Chinese expert consensus on the diagnosis of MC by the Chinese Society of Infectious Diseases and Cerebrospinal Fluid Cytology, and the diagnosis of MC was confirmed by CSF cytology. The control group included 10 patients who were diagnosed as autoimmune encephalitis or viral encephalitis. CSF mNGS and CNV analysis were performed simultaneously in all the patients.Results:Of the 10 patients with MC, 6 had lung adenocarcinoma, 4 had breast cancer. CSF mNGS and CNV analysis detected large CNV in 8 of 10 patients with MC, including 4 patients with breast cancer and 4 patients with lung cancer. The results of pathogenic microorganism analysis of CSF mNGS in all the patients were negative. Meanwhile, large CNV was not detected in the control group.Conclusions:CSF CNV can serve as a diagnostic marker for MC. The combination of mNGS and CNV analysis has demonstrated a high positive rate in the diagnosis of MC. The dual-omics analysis of pathogenic microorganisms and CNV has been proposed as a potential strategy to further expand the clinical utility of CSF mNGS in the realm of auxiliary diagnosis.

The role of fluid biomarkers in the diagnosis of Alzheimer′s disease / 中华神经科杂志

The rapid advancement of biomarker research in Alzheimer′s disease (AD) has improved the accuracy of AD diagnosis, facilitated its early diagnosis and intervention, and has significant implications for disease-modifying therapy research and evaluation. Since its introduction, the AT(N) system has grown in importance in both the clinical and research aspects of AD. However, the fluid biomarkers in the AT(N) system do not yet adequately reflect the complex pathophysiology of AD. Other fluid biomarkers associated with neuroinflammation, synaptic dysfunction, and vascular dysfunction should be a valuable addition to the AT(N). In recent years, the development and application of peripheral blood biomarkers have greatly enriched the fluid biomarker system for AD and are expected to greatly facilitate early screening and diagnosis of the disease. Here, a brief overview of current research on AT(N) and other pathogenesis-related fluid biomarkers is presented, and the article proposes that fluid biomarkers for AD should be studied from a variety of pathophysiological perspectives in order to improve their role in disease diagnosis. This article also discusses the role and limitations of fluid biomarkers in the diagnosis of AD, as well as the future development and application of fluid biomarkers in AD.

Spontaneous intracranial hypotension caused by high-flow spinal cerebrospinal fluid leaks: analysis of 6 patients / 中华神经科杂志

Objective:To analyze the clinical features of 6 patients with spontaneous intracranial hypotension caused by high-flow spinal cerebrospinal fluid leaks.Methods:The clinical characteristics, auxiliary examinations, treatment, and outcomes in 6 patients of spontaneous intracranial hypotension caused by high-flow spinal cerebrospinal fluid leaks enrolled in the Xuanwu Hospital, Capital Medical University from February 2021 to April 2022 were retrospectively reviewed.Results:All the 6 patients had orthostatic headaches. Brain magnetic resonance imaging showed dural enhancement and brain sagging and magnetic resonance myelography showed longitudinal extradural collection in all the patients. The high-flow spinal cerebrospinal fluid leaks were demonstrated in upper thoracic segments by the dynamic myelography. The headache disappeared after conservative treatment in 2 patients and treatment with targeted epidural blood patch in 4 patients.Conclusions:The diagnosis of spontaneous intracranial hypotension caused by high-flow spinal cerebrospinal fluid leaks with typical orthostatic headache and brain magnetic resonance imaging and myelography findings is not difficult. However, the localization of the site of high-flow spinal cerebrospinal fluid leaks in spontaneous intracranial hypotension depends on the dynamic myelography. Targeted epidural blood patch is effective, but conservative treatment does not always work.

Analysis of the clinical characteristics of 8 cases of spontaneous intracranial hypotension / 中华全科医师杂志

Objective:To analyze the clinical characteristics of patients with spontaneous low intracranial pressure (SIH).Methods:The study is a retrospective series. The clinical data of patients with SIH who visited Beijing Hospital from May 2017 to March 2022, including gender, age, symptoms, signs, imaging findings, treatment and outcome, were collected and their clinical characteristics were analyzed.Results:Finally, 8 patients with SIH, 6 females and 2 males, aged (33.5±7.3) years, were included. There were 6 cases of acute onset, 1 case of subacute onset, and 1 case of chronic onset. Four cases had pre-onset triggers, 3 cases were exertional and 1 case was exercise. All 8 cases had orthostatic headache. Three cases were accompanied by neck pain. Six cases were accompanied by autonomic dysfunction, 1 case with blurred vision and neck resistance, and 1 case with tinnitus in both ears. There were no obvious abnormalities in blood routine, liver and kidney function, electrolytes, and coagulation function in 8 cases. The results of the lumbar puncture showed that the cerebrospinal fluid pressure was≤60 mmH 2O(1 mmH 2O=0.009 8 kPa) in 7 cases, and 2 cases were so low that they were undetectable. One patient had normal cerebrospinal fluid pressure (90 mmH 2O). The routine results of cerebrospinal fluid showed 4 cases of an increased number of red blood cells and 2 cases of leukocytosis. The biochemical results of cerebrospinal fluid in all 8 cases were normal. All 8 patients underwent non-contrast MRI scan of the head, and 6 cases found abnormalities, including 2 cases of subdural hematoma, 1 case of subarachnoid hemorrhage, 1 case of brain tissue sinking, and 3 cases of intracranial venous sinus dilation (including 1 case with subdural hematoma). All 8 patients underwent MRI enhancement scan of the head, and 5 patients showed diffuse dural enhancement. Three patients underwent digital subtraction angiography myelogram and computed tomography myelogram, and 2 cases found dural cerebrospinal fluid leakage. One patient underwent magnetic resonance water imaging and no cerebrospinal fluid leakage was found. Eight patients were followed up for 38.5 (10.3, 63.0) months, after conservative treatment, 6 cases of headache relief or disappearance, 1 case relapsed and was admitted 1 week after discharge, non-targeted epidural blood patching (EBP) did not relapse, 1 case underwent non-targeted EBP after conservative treatment failure, headache relief, recurrence after 2 months, thoracic spine 3-4 space targeted EBP, headache disappeared, did not recur. Conclusions:The present study indicate that SIH prevalence in young age is common, the main symptom is orthostatic headache, accommodated with multiple clinical symptoms with various imaging abnormalities. Most patients with SIH can be treated conservatively, if the effect is not good, non-targeted or targeted EBP is feasible.