RESUMO
INTRODUCTION: Cerebrospinal fluid (CSF) analysis is important for detecting inflammation of the nervous system and the meninges, bleeding in the area of the subarachnoid space that may not be visualized by imaging, and the spread of malignant diseases to the CSF space. In the diagnosis and differential diagnosis of neurodegenerative diseases, the importance of CSF analysis is increasing. Measuring the opening pressure of CSF in idiopathic intracranial hypertension and at spinal tap in normal pressure hydrocephalus constitute diagnostic examination procedures with therapeutic benefits.Recommendations (most important 3-5 recommendations on a glimpse): The indications and contraindications must be checked before lumbar puncture (LP) is performed, and sampling CSF requires the consent of the patient.Puncture with an atraumatic needle is associated with a lower incidence of postpuncture discomfort. The frequency of postpuncture syndrome correlates inversely with age and body mass index, and it is more common in women and patients with a history of headache. The sharp needle is preferably used in older or obese patients, also in punctures expected to be difficult.In order to avoid repeating LP, a sufficient quantity of CSF (at least 10 ml) should be collected. The CSF sample and the serum sample taken at the same time should be sent to a specialized laboratory immediately so that the emergency and basic CSF analysis program can be carried out within 2 h.The indication for LP in anticoagulant therapy should always be decided on an individual basis. The risk of interrupting anticoagulant therapy must be weighed against the increased bleeding risk of LP with anticoagulant therapy.As a quality assurance measure in CSF analysis, it is recommended that all cytological, clinical-chemical, and microbiological findings are combined in an integrated summary report and evaluated by an expert in CSF analysis. CONCLUSIONS: In view of the importance and developments in CSF analysis, the S1 guideline "Lumbar puncture and cerebrospinal fluid analysis" was recently prepared by the German Society for CSF analysis and clinical neurochemistry (DGLN) and published in German in accordance with the guidelines of the AWMF (https://www.awmf.org). /uploads/tx_szleitlinien/030-141l_S1_Lumbalpunktion_und_Liquordiagnostik_2019-08.pdf). The present article is an abridged translation of the above cited guideline. The guideline has been jointly edited by the DGLN and DGN.
RESUMO
There is no other field of neurology where clinically relevant serological biomarkers have witnessed a surge in importance over the past decade resembling that in autoimmune encephalitis and cerebellitis. A multitude of newly discovered neuronal autoantibodies facilitate early diagnosis, estimation of prognosis, and therapeutic decision-making. However, this has led to growing uncertainty with regard to meaningful patient selection, the appropriate extent of testing, and management of seronegative cases. This review summarizes the essential aspects of the clinical presentation, diagnostic work-up, pathophysiology, and treatment of autoimmune encephalitis and cerebellitis.
Assuntos
Autoanticorpos/sangue , Biomarcadores/sangue , Doenças Cerebelares/diagnóstico , Doenças Cerebelares/terapia , Encefalite/diagnóstico , Encefalite/terapia , Doença de Hashimoto/diagnóstico , Doença de Hashimoto/terapia , Doenças Cerebelares/sangue , Diagnóstico Diferencial , Encefalite/sangue , Medicina Baseada em Evidências , Doença de Hashimoto/sangueRESUMO
INTRODUCTION: Limbic encephalitis (LE) associated with voltage-gated potassium channel-complex antibodies (VGKC-LE) is frequently non-paraneoplastic and associated with marked improvement following corticosteroid therapy. Mesial temporal lobe abnormalities are present in around 80 % of patients. If associated or preceded by faciobrachial dystonic seizures, basal ganglia signal changes may occur. In some patients, blurring of the supratentorial white matter on T2-weighted images (SWMB) may be seen. The purpose of this study was to evaluate the incidence of SWMB and whether it is specific for VGKC-LE. METHODS: Two experienced neuroradiologists independently evaluated signal abnormalities on FLAIR MRI in 79 patients with LE while unaware on the antibody type. RESULTS: SWMB was independently assessed as present in 10 of 36 (28 %) compared to 2 (5 %) of 43 non-VGKC patients (p = 0.009). It was not related to the presence of LGI1 or CASPR2 proteins of VGKC antibodies. MRI showed increased temporomesial FLAIR signal in 22 (61 %) VGKC compared to 14 (33 %) non-VGKC patients (p = 0.013), and extratemporomesial structures were affected in one VGKC (3 %) compared to 11 (26 %) non-VGKC patients (p = 0.005). CONCLUSION: SWMB is a newly described MRI sign rather specific for VGKC-LE.
Assuntos
Cérebro/patologia , Imagem de Tensor de Difusão/métodos , Encefalite Límbica/imunologia , Encefalite Límbica/patologia , Canais de Potássio de Abertura Dependente da Tensão da Membrana/imunologia , Substância Branca/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Autoanticorpos/imunologia , Cérebro/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Substância Branca/imunologia , Adulto JovemRESUMO
Cerebrospinal fluid (CSF) analysis is of utmost importance to establish an early diagnosis of central nervous system (CNS) infections and to start appropriate therapy. The CSF white cell count, lactate concentration and total protein levels are usually available very quickly even from non-specialized laboratories and the combination of these parameters often provides sufficient information for decision-making in emergency cases. It is, however, not always possible to identify the underlying infective agent despite further CSF analyses, such as bacterial and fungal staining, evaluation of the blood-CSF barrier function, intrathecal immunoglobulin synthesis and oligoclonal IgG bands. Therefore, close communication between the laboratory and the clinician is an important prerequisite to specify additional pathogen-related diagnostic measures for successful confirmation of the diagnosis.
Assuntos
Infecções do Sistema Nervoso Central/líquido cefalorraquidiano , Infecções do Sistema Nervoso Central/diagnóstico , Anticorpos/líquido cefalorraquidiano , Neoplasias do Sistema Nervoso Central/líquido cefalorraquidiano , Neoplasias do Sistema Nervoso Central/diagnóstico , Líquido Cefalorraquidiano/citologia , Proteínas do Líquido Cefalorraquidiano/líquido cefalorraquidiano , Comportamento Cooperativo , Diagnóstico Diferencial , Encefalite/líquido cefalorraquidiano , Encefalite/diagnóstico , Humanos , Imunoglobulinas/líquido cefalorraquidiano , Comunicação Interdisciplinar , Ácido Láctico/líquido cefalorraquidiano , Contagem de Leucócitos , Neuroborreliose de Lyme/líquido cefalorraquidiano , Neuroborreliose de Lyme/diagnóstico , Meningite/líquido cefalorraquidiano , Meningite/diagnóstico , Reação em Cadeia da Polimerase , Valor Preditivo dos Testes , Punção Espinal , Tuberculose do Sistema Nervoso Central/líquido cefalorraquidiano , Tuberculose do Sistema Nervoso Central/diagnósticoRESUMO
The mouse hippocampal cell line HT22 is an excellent model for studying the consequences of endogenous oxidative stress. Addition of extracellular glutamate depletes the cells of glutathione (GSH) by blocking the glutamate-cystine antiporter system x(c)(-). GSH is the main antioxidant in neurons and its depletion induces a well-defined program of cell death called oxytosis, which is probably synonymous with the iron-dependent form of non-apoptotic cell death termed ferroptosis. Oxytosis is characterized by an increase of reactive oxygen species and a strong calcium influx preceding cell death. We found a significant reduction in store-operated calcium entry (SOCE) in glutamate-resistant HT22 cells caused by downregulation of the Ca(2+) channel ORAI1, but not the Ca(2+) sensors STIM1 or STIM2. Pharmacological inhibition of SOCE mimicked this protection similarly to knockdown of ORAI1 by small interfering RNAs. Long-term calcium live-cell imaging after induction of the cell death program showed a specific reduction in Ca(2+)-positive cells by ORAI1 knockdown. These results suggest that dysregulated Ca(2+) entry through ORAI1 mediates the detrimental Ca(2+) entry in programmed cell death induced by GSH depletion. As this detrimental Ca(2+) influx occurs late in the course of the cell death program, it might be amenable to therapeutic intervention in diseases caused by oxidative stress.
Assuntos
Canais de Cálcio/metabolismo , Cálcio/metabolismo , Membrana Celular/metabolismo , Estresse Oxidativo , Animais , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Canais de Cálcio/química , Canais de Cálcio/genética , Linhagem Celular , Glutationa/metabolismo , Glicoproteínas de Membrana/antagonistas & inibidores , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Camundongos , Proteína ORAI1 , RNA Interferente Pequeno/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Molécula 1 de Interação Estromal , Molécula 2 de Interação EstromalRESUMO
Selecting neuronal cell lines for resistance against oxidative stress might recapitulate some adaptive processes in neurodegenerative diseases where oxidative stress is involved like Parkinson's disease. We recently reported that in hippocampal HT22 cells selected for resistance against oxidative glutamate toxicity, the cystine/glutamate antiporter system x(c)(-), which imports cystine for synthesis of the antioxidant glutathione, and its specific subunit, xCT, are upregulated. (Lewerenz et al., J Neurochem 98(3):916-25). Here, we show that in these glutamate-resistant HT22 cells upregulation of xCT mediates glutamate resistance, and xCT expression is induced by upregulation of the transcription factor ATF4. The mechanism of ATF4 upregulation consists of a 13 bp deletion in the upstream open reading frame (uORF2) overlapping the ATF4 open reading frame. The resulting uORF2-ATF4 fusion protein is efficiently translated even at a low phosphorylation levels of the translation initiation factor eIF2α, a condition under which ATF4 translation is normally suppressed. A similar ATF4 mutation associated with prominent upregulation of xCT expression was identified in PC12 cells selected for resistance against amyloid ß-peptide. Our data indicate that ATF4 has a central role in regulating xCT expression and resistance against oxidative stress. ATF4 mutations might have broader significance as upregulation of xCT is found in tumor cells and associated with anticancer drug resistance.
Assuntos
Fator 4 Ativador da Transcrição/genética , Fator 4 Ativador da Transcrição/metabolismo , Sistema y+ de Transporte de Aminoácidos/metabolismo , Neurônios/metabolismo , Estresse Oxidativo/fisiologia , Sistema y+ de Transporte de Aminoácidos/genética , Sistemas de Transporte de Aminoácidos Acídicos , Animais , Western Blotting , Linhagem Celular , Ensaio de Desvio de Mobilidade Eletroforética , Glutationa , Camundongos , Mutação , Estresse Oxidativo/genética , Células PC12 , Ratos , Reação em Cadeia da Polimerase Via Transcriptase ReversaAssuntos
Imunossupressores/uso terapêutico , Mielite Transversa/tratamento farmacológico , Mielite Transversa/imunologia , Idoso , Antígenos de Neoplasias/imunologia , Ciclofosfamida/uso terapêutico , Feminino , Humanos , Proteínas do Tecido Nervoso/imunologia , Antígeno Neuro-Oncológico Ventral , Proteínas de Ligação a RNA/imunologia , Esteroides/uso terapêuticoRESUMO
POEMS/Crow-Fukase syndrome is a rare multisystem disorder associated with elevated vascular endothelial growth factor (VEGF), which clinically presents with polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes. We report a case of POEMS syndrome due to a gammopathy of undetermined significance with thrombocytosis, vitamin B(12) deficiency, highly elevated VEGF and in addition to glomeruloid angiomas two previously undescribed proliferative vascular lesions: a spinal arteriovenous fistula and a plexogenic pulmonary arteriopathy, which ultimately resulted in lethal pulmonary hypertension. We assume that the high VEGF levels caused the vascular abnormalities observed in our patient.
Assuntos
Síndrome POEMS/complicações , Trombocitose/complicações , Doenças Vasculares/complicações , Deficiência de Vitamina B 12/complicações , Adulto , Fístula Arteriovenosa/complicações , Feminino , Humanos , Pulmão/irrigação sanguínea , Pulmão/patologia , Pneumopatias/complicações , Pneumopatias/patologia , Síndrome POEMS/sangue , Síndrome POEMS/patologia , Síndrome POEMS/fisiopatologia , Paraproteinemias/complicações , Paraproteinemias/fisiopatologia , Medula Espinal/irrigação sanguínea , Medula Espinal/patologia , Doenças da Medula Espinal/complicações , Doenças da Medula Espinal/patologia , Doenças Vasculares/patologia , Fator A de Crescimento do Endotélio Vascular/sangueRESUMO
An expression sequence tag identified in a screen for genes upregulated by retinoic acid induced neuronal differentiation of the human teratocarcinoma cell line Ntera2/D1 was found in close genomic proximity to a region of high sequence homology to the septin subfamily of GTPase genes. We could show that the tag corresponds to the 3' untranslated region of this novel gene named septin 3 and cloned three isoforms A (2191 bp), B (4378 bp), and C (1896 bp) from human Ntera2/D1 cDNA. We present the genomic localization and organization on chromosome 22q13.2, a chromosomal hot spot for translocations implicated in leukemia. Interestingly, MSF the closest paralog of septin 3 is a fusion partner in a therapy-related acute myeloid leukemia. Quantitative PCR confirmed the upregulation of the putative septin by neuronal differentiation and northern blotting showed only one band corresponding to sep3B with a neurospecific expression pattern in adult human tissues.
Assuntos
Cromossomos Humanos Par 22/genética , GTP Fosfo-Hidrolases/metabolismo , Neurônios/metabolismo , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Clonagem Molecular , GTP Fosfo-Hidrolases/genética , Humanos , Dados de Sequência Molecular , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Neurônios/citologia , Especificidade de Órgãos , Filogenia , Mapeamento Físico do Cromossomo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Septinas , Homologia de Sequência de Aminoácidos , Teratocarcinoma/genética , Teratocarcinoma/metabolismo , Tretinoína/farmacologia , Células Tumorais CultivadasRESUMO
The human teratocarcinoma cell line NTERA-2 cl.D1 (NT2 cells) can be induced with retinoic acid and cell aggregation to yield postmitotic neurones. This seems to model the in vivo situation, as high concentrations of retinoic acid, retinoic acid binding proteins, and receptors have been detected in the embryonic CNS and the developing spinal cord suggesting a role for retinoic acid in neurogenesis. Suppression subtractive hybridization was used to detect genes up-regulated by this paradigm of neuronal differentiation. Microfibril-associated glycoprotein 2 was found to be drastically up-regulated and has not been implicated in neuronal differentiation before. Suppression subtractive hybridization also identified DYRK4, a homologue of the Drosophila gene minibrain. Minibrain mutations result in specific defects in the development of the fly central nervous system. In adult rats, DYRK4 is only expressed in testis, but our results suggest an additional role for DYRK4 in neuronal differentiation. We have shown that suppression subtractive hybridization in conjunction with an efficient screening procedure is a valuable tool to produce a repertoire of differentially expressed genes and propose a new physiological role for several identified genes and expressed sequence tags.
Assuntos
Genes/fisiologia , Neurônios/fisiologia , Células-Tronco/citologia , Células-Tronco/fisiologia , Tretinoína/farmacologia , Northern Blotting , Diferenciação Celular , Linhagem Celular , Expressão Gênica , Humanos , Neurônios/citologia , Neurônios/efeitos dos fármacos , Reação em Cadeia da Polimerase , Células-Tronco/efeitos dos fármacos , Regulação para CimaRESUMO
In its usual form, school sports is neither calculated to motivate a lifelong pursuance of sports, nor is it particularly suitable for primary prevention of coronary heart disease. In view of the multifactorial pathogenetic nature of this disease, school sports can be nothing more than an adjunctive prophylactic measure. Epidemiological studies have shown a high level of probability for the usefulness of physical exercise as a preventive measure in childhood and adolescence. However, the findings of sports-medical research on endurance sports must be taken into account. In a controlled study of Hamburg children covering a period of 3 years, it was shown that pupils with high self-esteem, which was particularly encouraged, have better pre-conditions for a lifelong interest in active sports.