RESUMEN
Affections of the central nervous system (CNS) rarely occur in Lyme neuroborreliosis (LNB). CNS manifestations can have residual neurological symptoms despite antibiotic treatment. We explored the spectrum of CNS affections in patients with LNB in a tertiary care center in a region endemic for Lyme borreliosis. We retrospectively included patients treated at a tertiary care center from January 2020-December 2021 fulfilling the case criteria for LNB as stated in the current German guideline on LNB. Clinical data, cerebrospinal fluid (CSF) findings and MRI imaging were collected. We included 35 patients with LNB, 24 with early manifestations and 11 with CNS-LNB. CNS-LNB patients had encephalomyelitis (n = 6) or cerebral vasculitis (n = 5). Patients with early LNB and CNS-LNB differed regarding albumin CSF/serum quotient and total protein in CSF. Duration from onset of symptoms until diagnosis was statistically significantly longer in patients with encephalomyelitis. MRI findings were heterogeneous and showed longitudinal extensive myelitis, perimedullar leptomeningeal enhancement, pontomesencephalic lesions or cerebral vasculitis. CNS-LNB can present with a variety of clinical syndromes and MRI changes. No clear pattern of MRI findings in CNS-LNB could be identified. The role of MRI consists in ruling out other causes of neurological symptoms.
Asunto(s)
Neuroborreliosis de Lyme , Imagen por Resonancia Magnética , Humanos , Neuroborreliosis de Lyme/diagnóstico por imagen , Neuroborreliosis de Lyme/líquido cefalorraquídeo , Neuroborreliosis de Lyme/diagnóstico , Imagen por Resonancia Magnética/métodos , Femenino , Masculino , Persona de Mediana Edad , Adulto , Estudios Retrospectivos , Anciano , Sistema Nervioso Central/diagnóstico por imagen , Sistema Nervioso Central/patología , Encefalomielitis/diagnóstico por imagen , Encefalomielitis/líquido cefalorraquídeo , Adulto Joven , Vasculitis del Sistema Nervioso Central/diagnóstico por imagenRESUMEN
BACKGROUND: Toscana virus (TOSV) is an arthropod-borne virus transmitted by phlebotomine sandflies (Phlebotomus sp.) widespread throughout the Mediterranean having the potential to cause meningoencephalitis in humans. In Germany, the vectors of TOSV are introduced recently and become endemic especially in Southwestern Germany. As TOSV is not investigated regularly in patients with meningoencephalitis, cases of TOSV-neuroinvasive disease may remain mostly undetected. METHODS: We conducted a retrospective cohort study on patients with meningoencephalitis without identification of a causal pathogen from 2006 to 2016. Serologic assessment for anti-TOSV-IgG and IgM was performed on serum and CSF. Demographic, clinical and CSF data from TOSV-positive patients were compared to a cohort of patients with meningoencephalitis due to enterovirus. Informed consent was obtained from all included patients. RESULTS: We found 138 patients with meningoencephalitis without identified causal pathogen. From 98 of these patients CSF and serum was available for further testing. Additionally, we included 27 patients with meningoencephalitis due to enterovirus. We identified two patients with serological confirmed TOSV-neuroinvasive disease (TOSV-IgM and IgG positive, 2%) and two patients with possible TOSV-neuroinvasive disease (isolated TOSV-IgM positive, 2%). Overall, TOSV-neuroinvasive was detected in 4% of our cases with suspected viral meningoencephalitis. None of them had a history of recent travel to an endemic area. CONCLUSIONS: We found cases of TOSV-neuroinvasive disease in our German cohort of patients with meningoencephalitis. As no recent history of travel to an endemic area was reported, it remains probable that these cases resemble autochthonous infections, albeit we cannot draw conclusions regarding the origin of the respective vectors. TOSV could be considered in patients with meningoencephalitis in Germany.
Asunto(s)
Infecciones por Bunyaviridae , Meningoencefalitis , Virus de Nápoles de la Fiebre de la Mosca de los Arenales , Anticuerpos Antivirales , Alemania/epidemiología , Humanos , Inmunoglobulina G , Meningoencefalitis/epidemiología , Estudios RetrospectivosRESUMEN
About 5-20% of the general population in endemic areas have seroprevalence for anti-borrelial antibodies. Previous studies have shown a high rate of 25-97% of persisting anti-borrelial antibodies in patients with treated Lyme neuroborreliosis (LNB) at follow-up. These studies used immunoblots with antigens from whole-cell sonicates, which could be less specific than modern recombinant antigens. We assessed the seroprevalence of anti-borrelial antibodies in serum from patients with definite LNB and healthy controls with a line immunoblot using highly specific recombinant antigens. We retrospectively identified patients with treated definite LNB who were treated at the Medical Center-University of Freiburg. Serum from LNB patients at a mean follow-up period of 4.9 years (SD: 3.3) and serum from healthy controls were assessed for anti-borrelial antibodies with a line immunoblot with recombinant antigens. A total of 45 patients with definite LNB and 40 healthy controls were included. Ten LNB patients (22.7%) had persisting antibodies (IgG and/or IgM) in serum at follow-up. Serum samples from six healthy controls (15%) were positive for anti-borrelial antibodies (IgG and or IgM). Prevalence of positive IgM or IgG antibodies showed no statistically significant difference between LNB patients at follow-up and healthy controls (IgM p = 0.32, IgG p = 0.54). Immunoblot reactivity patterns at follow-up in LNB patients did not have statistically significant differences from healthy controls. The discrepancy regarding earlier studies reporting higher amounts of LNB patients with persisting antibodies could be due to a higher specificity of the antigens used in recombinant immunoblots compared to other immunoblots (e.g., whole-cell sonicates). The results of our study should be replicated in a larger prospective multi-center study.
Asunto(s)
Anticuerpos Antibacterianos/sangre , Antígenos Bacterianos/inmunología , Borrelia/inmunología , Neuroborreliosis de Lyme/epidemiología , Adulto , Anciano , Western Blotting , Femenino , Estudios de Seguimiento , Alemania/epidemiología , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Neuroborreliosis de Lyme/inmunología , Neuroborreliosis de Lyme/microbiología , Masculino , Persona de Mediana Edad , Proteínas Recombinantes/inmunología , Estudios Retrospectivos , Sensibilidad y Especificidad , Estudios SeroepidemiológicosRESUMEN
BACKGROUND: Cerebrospinal fluid (CSF) analysis is a crucial method in the diagnostic process for suspected subarachnoid hemorrhage (SAH), especially when cerebral imaging is negative or inconclusive. CSF cytology (detection of erythrophages or siderophages) is used to determine whether a bloodstained CSF resembles a genuine SAH. Whether erythrophages may develop in vitro after a traumatic puncture in case of delayed CSF analysis is unclear. An in vitro development of erythrophages after traumatic puncture would diminish the diagnostic properties of CSF analysis. We assessed whether erythrophagocytosis is detectable in CSF after an imitated traumatic lumbar puncture. METHODS: We mimicked a traumatic lumbar puncture by mixing surplus CSF with whole blood from the same patient. From this mixture, cytological specimens were obtained immediately and repeatedly at time intervals of 1 h, until 7 h after mixing, or until the mixture was exhausted. Each cytological specimen was microscopically examined independently by four experienced CSF cytologists for the presence of erythrophages. RESULTS: We studied 401 CSF cytological specimens of 96 punctures in 90 patients. We could not identify any erythrophages in all cytological specimens. Fleiss' Kappa for interrater-reliability was 1.0. CONCLUSIONS: We did not find evidence for an in vitro erythrophagocytosis after a mimicked traumatic lumbar puncture. Therefore, the occurrence of erythrophages in CSF cytology can be regarded as a reliable sign of an autochthonous bleeding in the subarachnoid space. Our results support the crucial role of CSF analysis in clinical practice in case of a suspected SAH but negative cerebral imaging.
Asunto(s)
Líquido Cefalorraquídeo/citología , Médula Espinal/citología , Hemorragia Subaracnoidea/sangre , Hemorragia Subaracnoidea/líquido cefalorraquídeo , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Técnicas In Vitro , Masculino , Persona de Mediana Edad , Punción EspinalRESUMEN
Lyme neuroborreliosis is a tick-borne infectious disease caused by the spirochete bacterium Borrelia burgdorferi sensu lato. Clinical manifestations are classified as early and late Lyme neuroborreliosis. Early manifestations are much more common than late manifestations. Serological testing should only be performed when typical neurological symptoms are present because false positive results are common due to a high seroprevalence in the population. Cerebrospinal fluid (CSF) analysis should be performed if Lyme neuroborreliosis is suspected. A systematic review found similar effects of beta-lactam antibiotics and doxycycline regarding the outcome of neurological symptoms and adverse effects. The prognosis after antibiotic treatment is usually favorable and residual symptoms can rarely persist. Impairments in quality of life, fatigue, depression and cognitive impairment are not more frequent in patients after treatment of Lyme neuroborreliosis than in the normal healthy population.
Asunto(s)
Antibacterianos/administración & dosificación , Borrelia/aislamiento & purificación , Líquido Cefalorraquídeo/microbiología , Doxiciclina/administración & dosificación , Neuroborreliosis de Lyme/diagnóstico , Neuroborreliosis de Lyme/terapia , beta-Lactamas/administración & dosificación , Borrelia/efectos de los fármacos , Diagnóstico Diferencial , Relación Dosis-Respuesta a Droga , Medicina Basada en la Evidencia , Humanos , Neuroborreliosis de Lyme/microbiología , Resultado del TratamientoRESUMEN
Lyme borreliosis is the most frequent tick-borne infection in Europe. It is a multisystemic disease affecting the skin, joints, heart, in rare cases the eyes and regularly the nervous system. Taking current clinical and microbiological guidelines into account, neuroborreliosis can in general be diagnosed and treated successfully. An appropriate guideline-conform antibiotic treatment is effective and in most cases recovery from acute neuroborreliosis is complete. Nevertheless, the evidence base regarding pharmacological treatment needs reform and improvement. Contrary to this scientifically based medical opinion, divergent opinions presented in the media cause uncertainty and confusion among patients and also some physicians. The currently available scientific data on epidemiology, treatment and performance of microbiological testing reveals gaps and therefore a large scope for interpretation. In clinical practice, diagnostics and therapeutic methods that do not fulfill the criteria of evidence-based medicine are widely used due to the uncertain data situation. The Clinical Network Neuroborreliosis (KNN) is a publicly funded network of clinicians and clinical laboratory physicians with the goal to improve knowledge for disease-oriented evaluation of diagnostic and therapeutic methods. In addition, the Robert Koch Institute (RKI) and the KNN are performing an epidemiological study for collation and estimation of the number of neuroborreliosis cases in Germany (aNBorD study).
Asunto(s)
Antibacterianos/uso terapéutico , Borrelia/efectos de los fármacos , Neuroborreliosis de Lyme/diagnóstico , Neuroborreliosis de Lyme/terapia , Diagnóstico Diferencial , Medicina Basada en la Evidencia , Alemania , Humanos , Neuroborreliosis de Lyme/líquido cefalorraquídeo , Resultado del TratamientoRESUMEN
INTRODUCTION: Antibodies against neurofascin, an axo-glial protein located around the node of Ranvier, have been shown to contribute to axonal pathology both in vitro and in experimental autoimmune encephalomyelitis models. Moreover, small case studies have reported anti-NF antibodies in samples from patients with progressive multiple sclerosis (MS). PATIENTS AND METHODS: Building up on this observation, we compared the anti-NF reactivity in serum samples from 83 chronic progressive MS (PMS) patients to those with relapsing remitting MS (RRMS, n=159) and 50 healthy controls. Anti-NF seroreactivity was quantified by enzyme-linked immunosorbent assay using recombinant rat neurofascin. In addition, to identify a potential intrathecal anti-NF antibody synthesis, we calculated the specific antibody index in paired cerebrospinal fluid and serum samples from MS patients with positive anti-NF seroreactivity. RESULTS: Prevalence of anti-NF seroreactivity in PMS patients (4.8%; all with primary progressive MS) was significantly higher than that detected in RRMS (0.6%; p=0.030). However, we found no significant difference between PMS patients and healthy controls (2.0%; p=0.408). MS patients with positive anti-NF reactivity experienced an above-average progression of disability compared to MS natural-history controls. Anti-NF-specific intrathecal antibody synthesis was not detected in MS patients with positive anti-NF seroreactivity. CONCLUSIONS: Although present only in a minor subgroup, seroprevalence of anti-NF reactivity was significantly more frequent in patients with PMS than in those with RRMS, but was also occasionally found in healthy controls. Further prospective studies are warranted to investigate whether anti-NF antibodies anticipate disease progression.
Asunto(s)
Anticuerpos/sangre , Moléculas de Adhesión Celular/inmunología , Esclerosis Múltiple/sangre , Esclerosis Múltiple/inmunología , Factores de Crecimiento Nervioso/inmunología , Adulto , Distribución de Chi-Cuadrado , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Estudios SeroepidemiológicosRESUMEN
Controversy exists about residual symptoms after pharmacological treatment of Lyme neuroborreliosis. Reports of disabling long-term sequels lead to concerns in patients and health care providers. We systematically reviewed the available evidence from studies reporting treatment of Lyme neuroborreliosis to assess the prevalence and spectrum of residual symptoms after treatment. A literature search was performed in three databases and three clinical trial registers to find eligible studies reporting on residual symptoms in patients after pharmacological treatment of LNB. Diagnosis must have been performed according to consensus-derived case definitions. No restrictions regarding study design or language were set. Symptom prevalence was pooled using a random-effects model. Forty-four eligible clinical trials and studies were found: 8 RCTs, 17 cohort studies, 2 case-control studies, and 17 case series. The follow-up period in the eligible studies ranged from 7 days to 20 years. The weighted mean proportion of residual symptoms was 28 % (95 % CI 23-34 %, n = 34 studies) for the latest reported time point. Prevalence of residual symptoms was statistically significantly higher in studies using the "possible" case definition (p = 0.0048). Cranial neuropathy, pain, paresis, cognitive disturbances, headache, and fatigue were statistically significantly lower in studies using the "probable/definite" case definition. LNB patients may experience residual symptoms after treatment with a prevalence of approximately 28 %. The prevalence and spectrum of residual symptoms differ according to the applied case definition. Symptoms like fatigue are not reported in studies using the "probable/definite" case definition. As the "possible" case definition is more unspecific, patients with other conditions may be included. Reports of debilitating fatigue and cognitive impairment after LNB, a "post-Lyme syndrome", could therefore be an artifact of unspecific case definitions in single studies.
Asunto(s)
Trastornos del Conocimiento/etiología , Enfermedades de los Nervios Craneales/etiología , Fatiga/etiología , Neuroborreliosis de Lyme/complicaciones , Dolor/etiología , Trastornos de la Sensación/etiología , Trastornos del Conocimiento/epidemiología , Enfermedades de los Nervios Craneales/epidemiología , Fatiga/epidemiología , Humanos , Neuroborreliosis de Lyme/tratamiento farmacológico , Neuroborreliosis de Lyme/epidemiología , Dolor/epidemiología , Trastornos de la Sensación/epidemiologíaRESUMEN
BACKGROUND: Many aspects of clinical management of Lyme neuroborreliosis are subject to intense debates. Guidelines show considerable variability in their recommendations, leading to divergent treatment regimes. The most pronounced differences in recommendations exist between guidelines from scientific societies and from patient advocacy groups. Assessment of the methodological quality of these contradictory guideline recommendations can be helpful for healthcare professionals. METHODS: Systematic searches were conducted in MEDLINE and databases of four international and national guideline organizations for guidelines on Lyme neuroborreliosis published from 1999-2014. Characteristics (e.g., year of publication, sponsoring organization) and key recommendations were extracted from each guideline. Two independent reviewers assessed the methodological quality of each guideline according to the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool. AGREE II scores from guidelines developed by scientific societies and from patient advocacy groups were compared across domains. RESULTS: We identified eight eligible guidelines of which n = 6 were developed by scientific societies and n = 2 by patient advocacy groups. Agreement on AGREE II scores was good (Cohen's weighted kappa = 0.87, 95% CI 0.83-0.92). Three guidelines, all from scientific societies, had an overall quality score of ≥ 50%. Two of them were recommended for use according to the AGREE II criteria. Across all guidelines, the AGREE II domain with the highest scores was "Clarity of Presentation" (65, SD 19%); all other domains had scores < 50% with the domain "Applicability" having the lowest scores (4, SD 4%). Guidelines developed by scientific societies had statistically significantly higher scores regarding clarity of presentation than guidelines from patient advocacy groups (p = 0.0151). No statistically significant differences were found in other domains. CONCLUSIONS: Current guidelines on Lyme neuroborreliosis vary in methodological quality and content. Health care providers and patients need to be aware of this variability in quality when choosing recommendations for their treatment decisions regarding Lyme neuroborreliosis. No statement can be given on quality of content and validity of recommendations, as these issues are not subject to assessment with the AGREE II tool and are prone to individual interpretation of the available evidence by the corresponding guideline panels. To enhance guideline quality, guideline panels should put more emphasis on linking recommendations to the available evidence, transparency in reporting how evidence was searched for and evaluated, and the implementation of recommendations into clinical practice.
Asunto(s)
Neuroborreliosis de Lyme , Guías de Práctica Clínica como Asunto/normas , Humanos , Sociedades CientíficasRESUMEN
BACKGROUND: So far, clinical studies in primary progressive MS (PPMS) have failed to meet their primary efficacy endpoints. To some extent this might be attributable to the choice of assessments or to the selection of the study population. OBJECTIVE: The aim of this study was to identify outcome influencing factors by analyzing the design and methods of previous randomized studies in PPMS patients without restriction to intervention or comparator. METHODS: A systematic literature search was conducted in MEDLINE, EMBASE, BIOSIS and the COCHRANE Central Register of Controlled Trials (inception to February 2015). Keywords included PPMS, primary progressive multiple sclerosis and chronic progressive multiple sclerosis. Randomized, controlled trials of at least one year's duration were selected if they included only patients with PPMS or if they reported sufficient PPMS subgroup data. No restrictions with respect to intervention or comparator were applied. Study quality was assessed by a biometrics expert. Relevant baseline characteristics and outcomes were extracted and compared. RESULTS: Of 52 PPMS studies identified, four were selected. Inclusion criteria were notably different among studies with respect to both the definition of PPMS and the requirements for the presence of disability progression at enrolment. Differences between the study populations included the baseline lesion load, pretreatment status and disease duration. The rate of disease progression may also be an important factor, as all but one of the studies included a large proportion of patients with a low progression rate. In addition, the endpoints specified could not detect progression adequately. CONCLUSION: Optimal PPMS study methods involve appropriate patient selection, especially regarding the PPMS phenotype and progression rate. Functional composite endpoints might be more sensitive than single endpoints in capturing progression.
Asunto(s)
Esclerosis Múltiple Crónica Progresiva/tratamiento farmacológico , Evaluación de Resultado en la Atención de Salud/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto , Proyectos de Investigación , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Selección de Paciente , Reproducibilidad de los ResultadosRESUMEN
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.
Asunto(s)
Cerebro/patología , Imagen de Difusión Tensora/métodos , Encefalitis Límbica/inmunología , Encefalitis Límbica/patología , Canales de Potasio con Entrada de Voltaje/inmunología , Sustancia Blanca/patología , Adulto , Anciano , Anciano de 80 o más Años , Autoanticuerpos/inmunología , Cerebro/inmunología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Sustancia Blanca/inmunología , Adulto JovenRESUMEN
BACKGROUND AND PURPOSE: Our aim was to evaluate the available evidence for pharmacological treatment of acute Lyme neuroborreliosis as a basis for evidence-based clinical recommendations in a systematic review. METHODS: A systematic literature search of Medline, EMBASE, the Cochrane Library and three trial registries was performed. Randomized controlled trials (RCTs) and non-randomized studies (NRS) were evaluated. Risk of bias was assessed using the Cochrane risk of bias tools. The primary outcome was 'residual neurological symptoms' whilst the secondary outcomes were disability, quality of life, pain, fatigue, depression, cognition, sleep, adverse events and cerebrospinal fluid pleocytosis. The quality of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: After screening 5779 records, eight RCTs and eight NRS were included. Risk of bias was generally high. No statistically significant difference was found between doxycycline and beta-lactam antibiotics in a meta-analysis regarding residual neurological symptoms at 4-12 months [risk ratio (RR) 1.27, 95% confidence interval (CI) 0.98-1.63, P = 0.07] or adverse events (RR 0.82, 95% CI 0.54-1.25, P = 0.35). Significantly fewer neurological symptoms for cefotaxime compared with penicillin were found (RR 1.81, 95% CI 1.10-2.97, P = 0.02). Adverse events were significantly fewer for penicillin (RR 0.56, 95% CI 0.38-0.84, P = 0.005). CONCLUSIONS: Evidence regarding pharmacological treatment of acute Lyme neuroborreliosis is scarce and therefore insufficient to recommend preference of beta-lactam antibiotics over doxycycline or vice versa. However, due to considerable imprecision, relevant differences between treatments cannot be excluded. No evidence suggesting benefits of extended antibiotic treatments could be identified. Further well-designed trials are needed. Individual treatment decisions should address patients' preferences and individual conditions like prior allergic reactions.
Asunto(s)
Antibacterianos/farmacología , Cefotaxima/farmacología , Doxiciclina/farmacología , Neuroborreliosis de Lyme/tratamiento farmacológico , Penicilinas/farmacología , beta-Lactamas/farmacología , Antibacterianos/administración & dosificación , Antibacterianos/efectos adversos , Cefotaxima/administración & dosificación , Cefotaxima/efectos adversos , Doxiciclina/administración & dosificación , Doxiciclina/efectos adversos , Femenino , Humanos , Penicilinas/administración & dosificación , Penicilinas/efectos adversos , beta-Lactamas/administración & dosificación , beta-Lactamas/efectos adversosRESUMEN
BACKGROUND: The chemokine CXCL13 has been discussed as a diagnostic parameter with high specificity for Lyme neuroborreliosis (LNB) and as a marker of disease activity. Neurosyphilis and LNB share similar characteristics. We investigated retrospectively CXCL13 levels in the cerebrospinal fluid (CSF) of patients with neurosyphilis at initial diagnosis and during treatment. RESULTS: Five patients with neurosyphilis were identified retrospectively using an electronic database in a tertiary care hospital from 2005 to 2012. CXCL13 levels were measured using an ELISA. Five patients with definite LNB and 10 patients with multiple sclerosis (MS) served as controls. Median CXCL13 levels at baseline were 972 pg/mL for neurosyphilis patients, 8,000 pg/mL for LNB patients, and 7.8 pg/mL for MS patients. Patients with LNB and neurosyphilis showed significantly higher CXCL13 levels in their CSF compared to MS patients (p < 0.05, p < 0.001, respectively). CXCL13 levels in the CSF declined during treatment. CONCLUSION: CXCL13 levels in the CSF of patients with neurosyphilis can be as high as in patients with LNB, exceeding the proposed threshold of 250 pg/mL for the diagnosis of LNB. Patients with encephalitic/myelitic syndromes appear to have especially high levels of CXCL13. Clinicians should be aware that high levels of CXCL13 are not found exclusively in LNB but also in other infectious diseases of the CNS.
Asunto(s)
Quimiocina CXCL13/análisis , Neurosífilis/líquido cefalorraquídeo , Neurosífilis/diagnóstico , Adulto , Anciano , Femenino , Humanos , Neuroborreliosis de Lyme/líquido cefalorraquídeo , Neuroborreliosis de Lyme/diagnóstico , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/líquido cefalorraquídeo , Esclerosis Múltiple/diagnóstico , Estudios RetrospectivosRESUMEN
OBJECTIVES: Presence of oligoclonal bands (OCB) in cerebrospinal fluid (CSF) is a diagnostic hallmark of multiple sclerosis (MS). However, up to 10% of patients were OCB negative in routine laboratory tests. The aim of this study was to determine whether there is at least an oligoclonal restriction of intrathecal antibody synthesis against measles, rubella and/or varicella zoster virus (MRZ-specific OCB) in CSF from oligoclonal bands-negative patients with MS. METHODS: CSF and serum samples from 17 well-defined OCB-negative patients with MS were analysed for MRZ-specific OCB. We performed isoelectric focusing (IEF) combined with affinity blotting using viral antigens, detection with a highly sensitive chemiluminescence technique and recording with X-ray films. Controls included 18 OCB-positive patients with MS and 11 patients with pseudotumor cerebri (PTC). RESULTS: Exclusive or predominant MRZ-specific OCB in CSF against at least one virus species were present in 8 of 17 patients with MS (47.1%; P = 0.0422), suggesting an oligoclonal intrathecal immune response, although OCB of total IgG were absent. Only a very weak oligoclonal reaction against varicella zoster virus in CSF from one of the PTC controls was detectable. Thirteen of 18 (72.2%; P = 0.0013) OCB-positive patients with MS showed also MRZ-specific oligoclonal bands against at least 1 neurotropic virus in CSF. CONCLUSIONS: MRZ-specific OCB argue for existence of a chronic intrathecal immune reaction also in routine laboratory-OCB-negative patients with MS. This phenomenon reflects oligoclonal restriction of the humoral immunoreaction as well as polyspecific intrathecal antibody synthesis, which are both characteristics in the chronic inflammatory process of MS.
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Anticuerpos Antivirales/líquido cefalorraquídeo , Esclerosis Múltiple/inmunología , Bandas Oligoclonales/líquido cefalorraquídeo , Adulto , Femenino , Humanos , Inmunoglobulina G/líquido cefalorraquídeo , Persona de Mediana Edad , Esclerosis Múltiple/líquido cefalorraquídeo , Rubéola (Sarampión Alemán)/inmunologíaAsunto(s)
Infecciones por Acinetobacter/complicaciones , Infecciones por Acinetobacter/etiología , Antibacterianos/uso terapéutico , Ventriculitis Cerebral/etiología , Coinfección , Colistina/uso terapéutico , Infecciones por Acinetobacter/tratamiento farmacológico , Acinetobacter baumannii/efectos de los fármacos , Antibacterianos/farmacología , Colistina/farmacología , Resistencia a Múltiples Medicamentos/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
Paraneoplastic neurological syndromes (PNS) are defined as remote effects on the central and peripheral nervous system that are not caused directly by the tumor, its metastases and treatment, or metabolic disorders. The most probable cause is a falsely initiated immune reaction. Well-defined classical PNSs are associated with distinct tumors and occur with onconeural antibodies directed against intracellular neuronal antigens. However, response to therapy is limited. Recently, new antibodies directed against neuronal surface antigens were described in encephalitic syndromes of autoimmune origin. These probably antibody-mediated disorders are more frequent than classical PNS, occur with or without tumor association and often show a good response to immunosuppressive treatment.
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Encefalopatías/diagnóstico , Enfermedad de Hashimoto/diagnóstico , Síndromes Paraneoplásicos del Sistema Nervioso/diagnóstico , Autoanticuerpos/sangre , Encefalopatías/inmunología , Encefalitis , Enfermedad de Hashimoto/inmunología , Humanos , Encefalitis Límbica/diagnóstico , Encefalitis Límbica/inmunología , Proteínas del Tejido Nervioso/inmunología , Degeneración Cerebelosa Paraneoplásica/diagnóstico , Degeneración Cerebelosa Paraneoplásica/inmunología , Síndromes Paraneoplásicos del Sistema Nervioso/inmunología , Trastornos Somatosensoriales/diagnóstico , Trastornos Somatosensoriales/inmunologíaRESUMEN
Paraneoplastic neurological syndromes (PNS) are very rare, remote effects of malignancies. Well-characterised antibodies against intracellular neuronal antigens are well-known in association with distinct tumors and with classical and non-classical syndromes. In this review article the current aspects of classification, pathophysiology, underlying tumors, antineuronal autoantibodies and diagnostic and therapeutic aspects of syndromes affecting the central nervous system are summarized.
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Autoanticuerpos/inmunología , Neoplasias del Sistema Nervioso Central/inmunología , Inmunoterapia/tendencias , Neuronas/inmunología , Síndromes Paraneoplásicos del Sistema Nervioso/diagnóstico , Síndromes Paraneoplásicos del Sistema Nervioso/terapia , Neoplasias del Sistema Nervioso Central/diagnóstico , Neoplasias del Sistema Nervioso Central/terapia , Diagnóstico Diferencial , Humanos , Síndromes Paraneoplásicos del Sistema Nervioso/inmunologíaRESUMEN
Recently, the disappearance of oligoclonal bands (OCBs) from the cerebrospinal fluid (CSF) of a few natalizumab-treated patients with multiple sclerosis (MS) has been reported. This is interesting since CSF-restricted OCB are believed to persist in MS. We pooled CSF data from 14 MS centers to obtain an adequate sample size for investigating the suspected changes in central nervous system (CNS)-restricted humoral immune activities in the context of natalizumab therapy. In a retrospective chart analysis, CSF parameters of blood-CSF barrier integrity and intrathecal IgG production from 73 natalizumab-treated MS patients requiring a diagnostic puncture for exclusion of progressive multifocal leukoencephalopathy were compared with CSF data obtained earlier in the course of disease before natalizumab therapy. At the time of repeat lumbar puncture, local IgG production (according to Reibergram) was significantly reduced (p < 0.0001) and OCB had disappeared in 16% of the patients. We therefore conclude that natalizumab therapy interferes with intrathecal antibody production at least in a significant number of patients.
Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Formación de Anticuerpos/efectos de los fármacos , Linfocitos B/inmunología , Inmunoglobulina G/líquido cefalorraquídeo , Esclerosis Múltiple/líquido cefalorraquídeo , Bandas Oligoclonales/líquido cefalorraquídeo , Adolescente , Adulto , Anciano , Linfocitos B/efectos de los fármacos , Femenino , Humanos , Inmunoglobulina G/inmunología , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/tratamiento farmacológico , Esclerosis Múltiple/inmunología , Natalizumab , Bandas Oligoclonales/efectos de los fármacos , Bandas Oligoclonales/inmunología , Estudios Retrospectivos , Adulto JovenRESUMEN
OBJECTIVES: SOX1 antibodies have been described in patients with Lambert-Eaton myasthenic syndrome (LEMS) in association with voltage-gated calcium channel antibodies as serological markers of small cell lung cancer (SCLC). This study was aimed to screen for additional SOX1 autoimmunity in onconeural antibody-positive sera from patients with paraneoplastic neurological syndromes (PNS) other than LEMS and to identify the clinical-immunological profile and associated tumours of patients with coexisting SOX1 antibodies. METHODS: We retrospectively analysed sera from 55 patients with different PNS positive for well-characterized antineuronal antibodies for the presence of SOX1 antibodies by recombinant ELISA and immunoblot. RESULTS: Eight (14.5%) patients showed additional SOX1 antibodies in the ELISA and the recombinant immunoblot. Five patients had coexisting Hu antibodies, while the other three showed coexisting CV2/CRMP5, amphiphysin, and coexisting CV2/CRMP5 and Hu antibodies, respectively. PNS included (partially overlapping) subacute sensory neuropathy, subacute sensorimotor neuropathy, cerebellar degeneration, brainstem encephalitis, encephalomyelitis and limbic encephalitis. No tumour was detected in two patients, while the others had lung cancer (four SCLC and two non-SCLC). One patient showed SOX1-specific intrathecal antibody synthesis. CONCLUSIONS: We describe SOX1 reactivity for the first time overlapping with CV2/CRMP5 and amphiphysin antibodies. SOX1 reactivity is predominantly associated with Hu antibodies and SCLC, but can occur also in other types of lung cancer. Neurological manifestations present in patients with coexisting SOX1 antibodies and well-characterized antineuronal antibodies do not differ from those previously described in patients positive for antineuronal antibodies but no SOX1-specific anti-glial antibodies.