Genetic Architecture and Functional Implications of the CSF-Contacting Nucleus / 神经科学通报·英文版

We previously identified a unique nucleus, the cerebrospinal fluid (CSF)-contacting nucleus. This study aims to understand its gene architecture and preliminarily suggest its functions. The results showed that there were about 19,666 genes in this nucleus, of which 913 were distinct from the dorsal raphe nucleus (non-CSF contacting). The top 40 highly-expressed genes are mainly related to energy metabolism, protein synthesis, transport, secretion, and hydrolysis. The main neurotransmitter is 5-HT. The receptors of 5-HT and GABA are abundant. The channels for Cl-, Na+, K+, and Ca2+ are routinely expressed. The signaling molecules associated with the CaMK, JAK, and MAPK pathways were identified accurately. In particular, the channels of transient receptor potential associated with nociceptors and the solute carrier superfamily members associated with cell membrane transport were significantly expressed. The relationship between the main genes of the nucleus and life activities is preliminarily verified.

Blood-cerebrospinal fluid (CSF) barrier dysfunction means reduced CSF flow not barrier leakage - conclusions from CSF protein data / Disfunção da barreira hemato-liquórica significa redução do fluxo de líquido cefalorraquidiano, e não quebra de barreira - conclusões a partir de estudos sobre as proteínas do LCR

ABSTRACT Background: Increased concentrations of serum proteins in cerebrospinal fluid (CSF) are interpreted as blood-CSF barrier dysfunction. Frequently used interpretations such as barrier leakage, disruption or breakdown contradict CSF protein data, which suggest a reduced CSF flow rate as the cause. Results: Even the severest barrier dysfunctions do not change the molecular size-dependent selectivity or the interindividual variation of the protein transfer across barriers. Serum protein concentrations in lumbar CSF increase with hyperbolic functions, but the levels of proteins that do not pass the barrier remain constant (brain proteins) or increase linearly (leptomeningal proteins). All CSF protein dynamics above and below a lumbar blockade can also be explained, independent of their barrier passage, by a reduced caudally directed flow. Local accumulation of gadolinium in multiple sclerosis (MS) is now understood as due to reduced bulk flow elimination by interstitial fluid (ISF). Nonlinear change of the steady state in barrier dysfunction and along normal rostro-caudal gradients supports the diffusion/flow model and contradicts obstructions of diffusion pathways. Regardless of the cause of the disease, pathophysiological flow blockages are found in bacterial meningitis, leukemia, meningeal carcinomatosis, Guillain-Barré syndrome, MS and experimental allergic encephalomyelitis. In humans, the fortyfold higher albumin concentrations in early fetal development decrease later with maturation of the arachnoid villi, i.e., with beginning CSF outflow, which contradicts a relevant outflow to the lymphatic system. Respiration- and heartbeat-dependent oscillations do not disturb net direction of CSF flow. Conclusion: Blood-CSF and blood-brain barrier dysfunctions are an expression of reduced CSF or ISF flow rate.

RESUMO Introdução: Concentrações aumentadas de proteínas séricas no líquido cefalorraquidiano são interpretadas como disfunção da barreira (hemato-liquórica) sanguínea do LCR. Interpretações frequentemente usadas, como vazamento de barreira (quebra ou rompimento de barreira), rompimento ou quebra, contradiz os dados de proteína do LCR, que sugerem uma taxa de fluxo reduzida do LCR como a causa. Resultados: Mesmo as disfunções de barreira mais graves não alteram a seletividade dependente do tamanho molecular nem a variação interindividual da transferência de proteína através de barreiras. As concentrações de proteínas séricas no LCR lombar aumentam com as funções hiperbólicas, mas as proteínas que não passam a barreira permanecem constantes (proteínas do cérebro) ou aumentam linearmente (proteínas leptomeningeais). Toda a dinâmica das proteínas do LCR acima e abaixo de um bloqueio lombar também pode ser explicada, independente de sua passagem pela barreira, por um fluxo caudal reduzido. O acúmulo local de gadolínio na esclerose múltipla (EM) é agora entendido como decorrente da redução da eliminação do bulk flow pelo fluido intersticial (FIS). A mudança não linear do estado estacionário na disfunção da barreira e ao longo dos gradientes rostro-caudais normais apoia o modelo de difusão/fluxo e contradiz as obstruções das vias de difusão. Independentemente da causa da doença, os bloqueios fisiopatológicos do fluxo são encontrados na meningite bacteriana, leucemia, carcinomatose meníngea, síndrome de Guillain-Barré, EM e encefalomielite alérgica experimental. Em humanos, as concentrações de albumina quarenta vezes mais altas no desenvolvimento fetal inicial diminuem tarde com a maturação das vilosidades aracnoides, isto é, com o início do fluxo de LCR, o que contradiz um fluxo relevante para o sistema linfático. As oscilações dependentes da respiração e do batimento cardíaco não perturbam a direção do fluxo do LCR. Conclusão: As disfunções das barreiras hemato-liquórica e hemato-encefálica são uma expressão da redução da taxa de fluxo do LCR ou FIS.

Importance of cerebrospinal fluid investigation during dengue infection in Brazilian Amazonia Region

BACKGROUND Amazon, the largest tropical forest of the world, has suffered from dengue outbreaks since 1998. Cerebrospinal fluid (CSF) of patients, from Amazonas state, suspected of central nervous system (CNS) viral infection was studied using molecular and immunological methods. OBJECTIVE To evaluate the importance of CSF investigation in patients with acute dengue virus (DENV) infection of CNS. METHODS CSF samples of 700 patients were analysed by reverse transcription polymerase chain reaction (RT-PCR) to detect the presence of dengue virus (DENV) RNA and by enzyme-linked immunosorbent assay (ELISA) to detect presence of DENV specific IgM. FINDINGS DENV infection was detected in 4.3% of the CSF samples; 85.7% (24/28) by DENV IgM and 14.3% (4/28) by viral RNA. DENV detected by viral RNA were to be found serotypes DENV-2 (three patients) and DENV-1 (one patient). The neurological diagnosis in patients CNS infection of DENV included encephalitis (10), meningoencephalitis (10), meningitis (6), acute myelitis (1), and encephalomyelitis (1). The majority (89.3%) had intrathecal inflammation: pleocytosis, hyperproteinorrachia and DENV IgM antibodies. Hypoglycorrhachia and/or high levels of lactate in CSF were found in 36% of the patients. Co-infection (CMV, HIV, EBV, and/or Mycobacterium tuberculosis) was observed in eight (28.6%) cases. CONCLUSIONS We found intense inflammatory CSF that is unusual in CNS disorders caused by dengue infection. It may be due co-infections or the immunogenetic background of the local Amerindian Brazilian population. CSF examination is an important diagnostic support tool for neurological dengue diagnosis.

Cerebrospinal fluid-contacting nucleus mediates nociception via release of fractalkine

Increasing evidence suggests that the cerebrospinal fluid-contacting nucleus (CSF-contacting nucleus) mediates the transduction and regulation of pain signals. However, the precise molecular mechanisms remain unclear. Studies show that release of fractalkine (FKN) from neurons plays a critical role in nerve injury-related pain. We tested the hypothesis that release of FKN from the CSF-contacting nucleus regulates neuropathic pain, in a chronic constriction injury rat model. The results show that FKN is expressed by neurons, via expression of its only receptor CX3CR1 in the microglia. The levels of soluble FKN (sFKN) were markedly upregulated along with the increase in FKN mRNA level in rats subjected to chronic constriction injury. In addition, injection of FKN-neutralizing antibody into the lateral ventricle alleviated neuropathic pain-related behavior followed by reduction in microglial activation in the CSF-contacting nucleus. The results indicate that inhibition of FKN release by the CSF-contacting nucleus may ameliorate neuropathic pain clinically.

Knowledge-base for interpretation of cerebrospinal fluid data patterns. Essentials in neurology and psychiatry / Bases do conhecimento para interpretação de padrões de dados em líquido cefalorraquidiano. Essenciais em neurologia e psiquiatria

ABSTRACT The physiological and biophysical knowledge base for interpretations of cerebrospinal fluid (CSF) data and reference ranges are essential for the clinical pathologist and neurochemist. With the popular description of the CSF flow dependent barrier function, the dynamics and concentration gradients of blood-derived, brain-derived and leptomeningeal proteins in CSF or the specificity-independent functions of B-lymphocytes in brain also the neurologist, psychiatrist, neurosurgeon as well as the neuropharmacologist may find essentials for diagnosis, research or development of therapies. This review may help to replace the outdated ideas like “leakage” models of the barriers, linear immunoglobulin Index Interpretations or CSF electrophoresis. Calculations, Interpretations and analytical pitfalls are described for albumin quotients, quantitation of immunoglobulin synthesis in Reibergrams, oligoclonal IgG, IgM analysis, the polyspecific ( MRZ- ) antibody reaction, the statistical treatment of CSF data and general quality assessment in the CSF laboratory. The diagnostic relevance is documented in an accompaning review.

RESUMO As bases do conhecimento biológico e biofísico para interpretação de dados do líquido cefalorraquidiano (LCR), assim como das faixas de referência, são essenciais para o patologista clínico e para o neuroquímico. Com a descrição popular da função de barreira dependente do fluxo LCR, a dinâmica e os gradientes de concentração das proteínas derivadas do sangue, do cérebro e da leptomeninge no LCR, bem como as funções específico-independentes dos linfócitos B no cérebro também podem ser essenciais para o diagnóstico ou o desenvolvimento de terapias pelo neurologista, psiquiatra, neurocirurgião e neurofarmacologista. Essa revisão pode auxiliar na substituição de conceitos ultrapassados como os dos modelos de “ruptura” das barreiras, das interpretações lineares do índice de imunoglobulina ou da eletroforese do LCR. Cálculos, interpretações e armadilhas analíticas são descritos para quocientes de albumina, quantificação da síntese de imunoglobulinas em Reibergramas, IgG oligoclonal, análise de IgM, reação MRZ (anticorpo poliespecífico), tratamento estatístico de dados do LCR e qualidade geral das análises no laboratório de LCR. A relevância do diagnóstico está documentada em uma revisão anexa a este documento.

Cerebrospinal fluid data compilation and knowledge-based interpretation of bacterial, viral, parasitic, oncological, chronic inflammatory and demyelinating diseases. Diagnostic patterns not to be missed in neurology and psychiatry / Liquido cefalorraquidiano: compilação dos dados e interpretação avançada de doenças bacterianas, virais, parasitarias, oncológicas, inflamatórias cronicas e desmielinizantes. Padrões diagnósticos que não devem faltar em neurologia e psiquiatria

ABSTRACT The analysis of intrathecal IgG, IgA and IgM synthesis in cerebrospinal fluid (CSF) and evaluation in combined quotient diagrams provides disease-related patterns. The compilation with complementary parameters (barrier function, i.e., CSF flow rate, cytology, lactate, antibodies) in a cumulative CSF data report allows a knowledge-based interpretation and provides analytical and medical plausibility for the quality assessment in CSF laboratories. The diagnostic relevance is described for neurological and psychiatric diseases, for which CSF analysis can’t be replaced by other diagnostic methods without loss of information. Dominance of intrathecal IgM, IgA or three class immune responses give a systematic approach for Facial nerve palsy, Neurotrypanosomiasis, Opportunistic diseases, lymphoma, Neurotuberculosis, Adrenoleucodystrophy or tumor metastases. Particular applications consider the diagnostic power of the polyspecific antibody response (MRZ-antibodies) in multiple sclerosis, a CSF-related systematic view on differential diagnostic of psychiatric diseases and the dynamics of brain- derived compared to blood-derived molecules in CSF for localization of paracytes.

RESUMO A análise da síntese intratecal de IgG, IgA e IgM no liquido cefalorraquidiano (LCR) e a avaliação destas em diagramas com quocientes sugere padrões de diversas doenças. Estes dados, juntamente com outros parâmetros como a função de barreira, o fluxo liquórico, a citologia, o lactato e a pesquisa de anticorpos, integrados em uma ficha de paciente, permite uma interpretação baseada em conhecimento e permite também uma aferição da qualidade em laboratórios de LCR. A relevância diagnóstica é descrita para doenças neurológicas e psiquiátricas pois a análise do LCR não pode ser substituída por outros metódos diagnósticos sem perda de informação para o diagnóstico do paciente. O aumento da síntese intratecal de IgM, IgA ou das 3 classes de imunoglobulinas sugerem um diagnóstico sistemático de paralisia facial periférica, neurotripanosomiase, doenças oportunísticas, linfoma, neurotuberculose, adrenoleucodistrofia ou metástases de tumores cerebrais. A resposta poliespecífica de anticorpos contra sarampo, rubéola e varicela zoster (MRZ reação) é sugestiva de esclerose múltipla. Uma visão sistemática considera o diagnóstico diferencial de doenças psiquiátricas e doenças chrônicas. A dinâmica de moléculas derivadas do cérebro comparadas com aqueles derivadas do sangue é importante para a localização de parasitos em doenças parasitárias do sistema nervoso.

Estudio del flujo del líquido cefalorraquídeo (LCR) con cine resonancia magnética (CINE RM) / Cerebrospinal fluid flow Study (LCR) with Cine Magnetic Resonance Imaging (CINE RM)

En el presente trabajo se analiza la experiencia preliminar en la Clínica Las Condes, referida a 69 pacientes. En su indicación predominó la evaluación del tipo de circulación de LCR en quistes aracnoidales, hidrocefalia y malformación de Chiari I con o sin siringomielia. Fue extremadamente útil en los quistes aracnoidales, siendo no comunicantes diez y comunicantes cuatro. En hidrocefalia, ayudó al diagnóstico gracias al flujo hiperdinámico de los ventrículos laterales, producido en esta patología. En la malformación de Chiari I ilustró en forma elegante el efecto pistón, su correción por la descompresiva occipitocervical y la duroplastía de expansión con aponeurosis de pericráneo. Demostró una gran utilidad en el control de funcionalidad de las tercerventrículocisternostomías.

Laparoscopic management of complicated ventriculoperitoneal shunts.

Intra-abdominal migration of the catheter and formation of a cerebrospinal fluid pseudocyst are both rare complications of a ventriculoperitoneal shunt. Traditionally, each condition is treated by a formal laparotomy. Laparoscopic management of the complications in two patients is described.

Enfermedad de Yme en areas presuntamente endemicas del departamento de Tarija-Bolivia / Lyme disease in Tarija-Bolivia

Pregunta de investigación. Existe la enfermedad de Lyme en Bolivia? Objetivo. Detenninar la existencia de la enfermedad de Lyme en un área presuntamente endémica Población. Habitantes de la Reserva Nacional de Hora y Fauna Tariquía Diseño. Estudio exploratorio y descriptivo. Material y Métodos. Se tomaron muestras previa entrevista personalizada, de tres puntos estratégicos de la Reserva en reuniones comunarias en las que estuvieron presentes los pobladores que conforman el Parque. Las muestras fueron sometidas a cuatro tipos de pruebas: dos de cribado con los métodos de enzimo inmuno ensayo e imnunofluorescencia indirecta. Una prueba confirmatoria con el método de inmunoblot para confirmar los casos positivos y la prueba de V.D.R.L. para descartar posibles reacciones cruzadas que pudiesen ocurrir entre Borrelia burgdorferi y Treponema pallidum. Resultados. Se encontraron cuatro casos confirmados de enfermedad de Lyme en la comunidad d Cbiquiacá y once casos de sífilis en toda el área de estudio Conclusiones. Se demuestra por primera vez, la presencia de la enfermedad de Lyme en nuestro medio, la que se debe dar a conocer y aplicar las medidas pertinentes para su control y tratamieno

Neuropsychiatric manifestations in Thai patients with systemic lupus erythematosus.

Neuropsychiatric (NP) manifestations in patients with systemic lupus erythematosus (SLE) [NPSLE] and prognostic factors were studied in 91 patients. There were 98 NP episodes, of which 78 (79.6%) occurred within the first year of the disease. Twenty-six patients (6.7%) had NPSLE as an initial presentation of the disease. There were seizures in 53 episodes (54.1%), psychosis in 13 (13.3%), acute confusion state in 11 (11.2%), abnormal consciousness in 6 (6.1%), transverse myelitis in 6 (6.1%), peripheral neuropathy in 5 (5.1%), cerebral infarction in 2 (2.0%) and aseptic meningitis in 2 (2.0%). Most forms of NPSLE responded well to high dose corticosteroids. Anti-convulsant therapy could be discontinued within a median duration of 3 months after the SLE activity was under control, and without significant recurrence of seizures. The 5-year and 10-year survival rates of patients with NPSLE were 75.9% and 50.6%, respectively. Patients with NPSLE had significantly more cutaneous vasculitis and less arthritis than those without.

Utilidad del ácido láctico en líquido cefalorraquideo en el diagnóstico de meningitis bacteriana / Usefulness of the lactic acid in cerebrospinal fluid in the diagnostic of meningitis bacterial

Con el fin de evaluar la utilidad del ácido en líquido cefalorraquídeo (LCR) para el diagnóstico de meningitis bacteriana, realizamos un estudio desde abril 1995 a julio 1996, en 71 pacientes que ingresararon al Servicio de Emergencia Pediátrica del Hospital "Dr. Domingo Luciani" por presentar hallazgos clínicos sugestivos de meningitis. El valor promedio del ácido láctico, obtenido por método inmunoenzimatico, en los pacientes con meningitis bacteriana fue de 8,86 mmol/l, y de 1,91 ñ 0,94 mmol/l en los pacientes con meningitis aséptica. La sensibilidad del ácido láctico fue del 92 por ciento y la especificación del 98 por ciento. Concluimos que el ácido láctico constituye un examen que puede ayudar en el diagnóstico precoz de certeza de la meningitis bacteriana así como en el diagnóstico diferencial con la aséptica

Líquido cefalorraquiano: aspectos anatômicos das principais estruturas envolvidas na sua formaçäo, circulaçäo e absroçäo / Cerebrospinal fluid: morphological aspects of the structure involved in the formation, circulation and absortion

Este trabalho teve por objetivo a atualizaçäo dos aspectos anatômicos das estruturas envolvidas na formaçäo, circulaçäo e absorçäo do líquido cefalorraquiano através de uma revisäo das publicaçöes científicas dos últimos dez anos, englobando os periódicos nacionais e internacionais disponíveis no Brasil.

Sindrome de Rett: a propósito de tres casos / Rett syndrome: report of three cases

Hemos estudiado y presentado a tres niñas con sindrome de Rett, el cual no tiene un tratamiento que pueda hacer remitir los síntomas y el deterioro es progresivo,, por lo que se considera es una encefalopatía. El tratamiento de sostén está destinado a mejorar su calidad de vida y prolongar la mayor independencia en actividades de la vida diaria y en nuestro medio; evitar tratamientos costosos multidisciplinarios. Más al contrario, intentamos orientar a la familia sobre la enfermedad de sus hijas y apoyamos el ingreso de las mismas a instituciones que se dedican a la educación y cuidado especial de los niños.

Tempo de gotejamento do líquido cefalorraquidiano com agulhas espinhais tipo Quincke / Time for cerebrospinal fluid backflow through Quinckle spinal needles

Background and objectives - Postdural puncture headache (PDPH) has discouraged many anesthesiologists to use spinal anesthesia, specially in young patients. It is accepted that PDPH results from the leakage of cerebrospinal fluid (CSF) to the epidural space, which is related to the size of the hole produced by the needle in the duramater. The purpose of this study was to evaluate the time for CSF backflow in healthy patients undergoing spinal anesthesia with 25G, 27G and 29G Quincke needles. Methods - Sixty-nine patients undergoing spinal anesthesia were included in the study and allocated into three groups according to the needle gauge (25G, 27G or 29G). Following subarachnoidal punctureand removal of the mandril, time to filling of the needle hub with CSF was observed. - Results - Time for CSF backflow through 29G needles was significantly longer as compared to that observed for 25G and 27G needles. No differences were observed between 25G and 27G needles. Conclusions - The literature reports increased anesthetic failure and further reduction of PDPH with 29G Quincke needles. Additionally, the prolonged backflow time through 29G needles observed in this study should encourege the use of 27G needles, wich are similar to 25G needles in the regard

Aspectos dos líquidos cefalorraquidianos nas meningites bacterianas / The cerebrospinal fluid in bacterial meningitis

Samples of 1815 cerebrospinal fluid (CSF) were studied in a meningitis outbreak during 1989 in S ao Paulo, Brazil. Neisseria meningitis 56 per cent with 44 per cent type B, Haemophilus influenzae 17 per cent , from which 72 per cent in children (days to 3-year-old) and Streptococcus pneumoniae 14 per cent from which 60 per cent in children (day to 1-year-old) of 443 (24 per cent ) of all strains. Cytochemistry study showed: purulent or turbidity aspects in 70 to 79 per cent positive bacterioscopy or culture of CSF; white cells count > 500/mm3; glucose < 45 mg/dl; protein > 90 mg/dl in 90 per cent of all patients. We concluded that: CSF prognostic factors: (aspect and cytochemistry) were correlated with bacterial meningitis. Bacterioscopy and positive cultures were correlated to NM, SP and HI isolation from these patients (Goodman Test)

Fístula liquórica traumática temporomalar com presença de corpo estranho / Traumatic temporomalar fistula with foreing bodies

Os autores relatam o caso de um paciente com traumatismo cranioencefálico devido a agressäo. Apresentou fístula liquórica de alto débito, através de ferimento na hemiface direita. Evoluiu com meningite, que foi tratada com antibiótico, porém a fístula permaneceu. O estudo tomográfico aliado a cisternografia demonstrou o trajeto fistuloso em topografia temporomalar à direita. Durante a cirurgia foi encontrado pedaço de madeira de 8x1cm, que estava no trajeto da fístula e penetrava no lobo temporal. Com o tratamento cirúrgico houve fechamento da fístula e resoluçäo do caso

Effect of indomethacin (a prostaglandin synthetase inhibitor) on the permeability of blood-brain and blood-CSF barriers in rat.

Effect of indomethacin on the permeability of blood-brain and blood-csf barriers to Evans blue, bromophenol blue and horseradish peroxidase (HRP) was studied by administering the drug through right internal carotid artery, right external jugular vein and through intraperitoneal route in rats. Increased permeability was observed on internal carotid arterial injection but not following jugular vein or intraperitoneal injection. This increased permeability of blood-brain and blood-csf barriers following injection of indomethacin into the internal carotid artery is associated with a steep and sustained rise in mean arterial blood pressure (MABP), a feature not observed in bilateral adrenalectromised animals.