Knowledge-base for interpretation of cerebrospinal fluid data patterns. Essentials in neurology and psychiatry.

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 This review may help to replace the outdated ideas like "leakage" models of the barriers, linear immunoglobulin Index Interpretations or CSF electrophoresis.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.

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 This review may help to replace the outdated ideas like “leakage” models of the barriers, linear immunoglobulin Index Interpretations or CSF electrophoresis.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.

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.

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.

Cerebrospinal fluid values for monoamine metabolites, gamma-aminobutyric acid, and other amino compounds in Rett syndrome.

We measured concentrations of 3-methoxy-4-hydroxy-phenylglycol, 3,4-dihydroxyphenylacetic acid, homovanillic acid, and 5-hydroxyindoleacetic acid--the metabolites of noradrenaline, dopamine, and serotonin used as central neurotransmitters--in the cerebrospinal fluid (CSF) specimens of five girls with Rett syndrome. These patients met the clinical criteria for both inclusion and exclusion of the diagnosis of Rett syndrome. In contrast to previous reports, cerebral monoamine metabolites were present in normal concentrations in CSF. In addition, concentrations of gamma-aminobutyric acid and of a large number of other amino acids and related compounds were normal in the CSF of patients with the syndrome. We doubt that an underlying biochemical cause for this disorder has yet been discovered.

Cuantificación de beta-endorfinas en pacients psiquiátricos sometidos a estimulación cerebelosa crónica con el aparato funcionando y sin funcionar / Quantification of beta-endorphins in psychiatric patients under cerebellar chronic stimulation in on and off state

En este estudio se discute la relación que existe entre las beta-endorfinas y la neuroestimulación, así como la posible relación entre las beta-endorfinas y algunas enfermedades psiquiátricas y de la conducta como agresividad, depresión y esquizofrenia. Se cuantificaron las concentraciones de estos péptidos en el líquido cefalorraquídeo (LCR) de diez individuos testigos y ocho pacientes psiquiátricos sometidos a estimulación cerebelosa crónica (ECC) en dos momentos experimentales: con el aparato funcionando y sin funcionar. No se encontraron diferencias estadísticamente significativas en las concentraciones de beta-endorfinas entre los sujetos del grupo testigo y los pacientes psiquiátricos (tres con epilepsia de lóbulo temporal y agresividad, dos con neurosis obsesivo compulsiva y depresión, y tres pacientes psicóticos con agresividad extrema y paranoia) cuando el aparato se encontraba sin funcionar. Por lo contrario, sí hubo una franca diferencia estadística (P < 0.05) cuando el aparato se encontraba funcionando. Estos resultados demuestran que la ECC incrementa las concentraciones de beta-endorfinas en el LCR, lo cual explica algunas observaciones clínicas como sensación de bienestar, cierta euforia, supresión del dolor, "adicción" a la neuroestimulación, supresión de síntomas psicóticos y de algunos trastornos de la conducta. La posibilidad de establecer una relación de causa o efecto entre el incremento de beta-endorfinas con las alteraciones psiquiátricas o con el efecto de los neuroestimuladores requiere aún de estudios ulteriores, pero parece factible