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Antirheumatic medication is of crucial importance within the treatment concept of chronic inflammatory disorders. Side effects may affect various organ systems, among which are neurologic manifestations. If patients have comorbidities involving the nervous system this should be taken into consideration before choosing an individual immunosuppressant or immunomodulatory compound, as any worsening of the underlying neurologic disease should be avoided. In this article, relevant neurologic disorders will be described with respect to the clinical manifestations, differential diagnosis and treatment. In the second part, pharmaceuticals and biologicals which are frequently used as part of an antirheumatic regimen are discussed with respect to the potential to induce side effects specifically related to the nervous system.
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Antirreumáticos/efeitos adversos , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Encefalopatias/induzido quimicamente , Encefalopatias/diagnóstico , Doenças do Sistema Nervoso/induzido quimicamente , Doenças do Sistema Nervoso/diagnóstico , Artrite Reumatoide/complicações , Encefalopatias/prevenção & controle , Diagnóstico Diferencial , Humanos , Doenças do Sistema Nervoso/prevenção & controleRESUMO
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.
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BACKGROUND: A polyspecific, intrathecal humoral immune response against neurotropic viruses such as measles, rubella and varicella zoster virus (MRZ reaction, MRZR) is present in 80-100% of patients with multiple sclerosis (MS), but has not to date been evaluated in patients with neuromyelitis optica (NMO). AIMS: To evaluate whether MRZR distinguishes NMO and MS. METHODS: 20 patients with NMO and 42 with MS were included. The intrathecal synthesis of antibodies against measles, rubella and varicella zoster virus was detected by calculation of the respective antibody indices (AI). RESULTS: A positive MRZ reaction, as defined by a combination of at least two positive AIs, was found in 37/42 MS, but in only 1/20 NMO patients (p<0.0001). Median AI values differed significantly between the groups (p<0.0005). CONCLUSIONS: The polyspecific antiviral humoral immune response characteristic for MS is widely missing in NMO, irrespective of the NMO-IgG status of the patients. Our findings further strengthen the case for NMO being pathologically distinct from MS.
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Anticorpos Antivirais/imunologia , Esclerose Múltipla/diagnóstico , Esclerose Múltipla/imunologia , Neuromielite Óptica/diagnóstico , Neuromielite Óptica/imunologia , Adulto , Idoso , Varicela/imunologia , Diagnóstico Diferencial , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Humanos , Imageamento por Ressonância Magnética , Masculino , Sarampo/imunologia , Pessoa de Meia-Idade , Nervo Óptico/imunologia , Nervo Óptico/patologia , Rubéola (Sarampo Alemão)/imunologiaRESUMO
OBJECTIVE: To study the time course of immunoglobulin, B and plasma cells in the blood and cerebrospinal fluid (CSF) before and during rituximab treatment in a patient with severe relapsing-remitting multiple sclerosis (MS) in relation to clinical and MRI findings. METHODS: Immunoglobulins in the CSF were measured by nephelometry and detected by isoelectrical focussing. CSF and blood cell subtypes from seven time points were analysed by flow cytometry. RESULTS: Treatment with rituximab induced a dramatic and sustained improvement in clinical and MRI findings over a follow-up period of 20 months. By contrast, the initially completely suppressed B and plasma cells in both the blood and CSF reappeared after 5 and 10 months, CSF cells being the first to reappear. Interestingly, intrathecal IgG synthesis persisted throughout the study period. DISCUSSION: Although highly effective in this case, the clinical effect in larger series and the mechanism of rituximab in MS deserves further evaluation.
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Anticorpos Monoclonais/uso terapêutico , Linfócitos B/imunologia , Imunoglobulina G/biossíntese , Esclerose Múltipla/tratamento farmacológico , Adulto , Anticorpos Monoclonais Murinos , Formação de Anticorpos , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/líquido cefalorraquidiano , Imageamento por Ressonância Magnética , Masculino , Esclerose Múltipla/diagnóstico , Esclerose Múltipla/imunologia , Plasmócitos/imunologia , Rituximab , Resultado do TratamentoRESUMO
In a 9-year-old boy with sudden sensorineural loss of hearing in the lower registers in both ears, serology showed elevated levels of antibodies against Borrelia burgdorferi and examination of the CSF revealed a positive antibody index against Borrelia burgdorferi. The boy was treated with antibiotics for 2 weeks. Audiometry performed 4 weeks after treatment was completely normal. Inner ear involvement in Lyme disease has often been discussed. Treating these patients with antibiotics may lead to an improvement in some.
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Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Neurossensorial/etiologia , Doenças do Labirinto/diagnóstico , Doenças do Labirinto/etiologia , Doença de Lyme/complicações , Doença de Lyme/diagnóstico , Criança , Humanos , MasculinoRESUMO
BACKGROUND: It has long been known that the majority of patients with multiple sclerosis (MS) display an intrathecal, polyspecific humoral immune response to a broad panel of neurotropic viruses. This response has measles virus, rubella virus and varicella zoster virus as its most frequent constituents and is thus referred to as the MRZ reaction (MRZR). OBJECTIVE: Re-evaluation of the specificity of MRZR as a marker of MS. METHODS: Structured review of the existing English-, German- and Spanish-language literature on MRZR testing, with evaluation of MRZR in a cohort of 43 unselected patients with MS and other neurological diseases as a proof of principle. RESULTS: A positive MRZ reaction, defined as a positive intrathecal response to at least two of the three viral agents, was found in 78% of MS patients but only in 3% of the controls (p < 0.00001), corresponding to specificity of 97%. Median antibody index values were significantly lower in non-MS patients (measles, p < 0.0001; rubella, p < 0.006; varicella zoster, p < 0.02). The 30 identified original studies on MRZR reported results from 1478 individual MRZR tests. A positive MRZR was reported for 458/724 (63.3%) tests in patients with MS but only for 19/754 (2.5%) tests in control patients (p < 0.000001), corresponding to cumulative specificity of 97.5% (CI 95% 96-98.4), cumulative sensitivity of 63.3% (CI 95% 59.6-66.8) (or 67.4% [CI 95% 63.5-71.1] in the adult MS subgroup), a positive likelihood ratio of 25.1 (CI 95% 16-39.3) and a negative likelihood ratio of 0.38 (CI 95% 0.34-0.41). Of particular note, MRZR was absent in 52/53 (98.1%) patients with neuromyelitis optica or MOG-IgG-positive encephalomyelitis, two important differential diagnoses of MS. CONCLUSION: MRZR is the most specific laboratory marker of MS reported to date. If present, MRZR substantially increases the likelihood of the diagnosis of MS. Prospective and systematic studies on the diagnostic and prognostic impact of MRZR testing are highly warranted.
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Anticorpos Antivirais/líquido cefalorraquidiano , Herpesvirus Humano 3/imunologia , Vírus do Sarampo/imunologia , Esclerose Múltipla/líquido cefalorraquidiano , Vírus da Rubéola/imunologia , Biomarcadores/líquido cefalorraquidiano , Humanos , Esclerose Múltipla/virologiaRESUMO
Abnormalities in T-cell-derived cytokine production are a well-known phenomenon in multiple sclerosis (MS). An association between disability and the production of interferon gamma has been demonstrated recently. The present study investigated associations between disability, cytokine production in stimulated blood lymphocytes and magnetic resonance imaging data in 37 patients with the secondary progressive course in the stable phase of the disease. Patients with high interleukin-10 (IL-10) production had significantly lower disability scores (p=0.009) and lower T2 lesion load (p=0.03). Interleukin-10 might not only play a role in the pathological process of multiple sclerosis but has an impact on disease outcome as well.
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Interleucina-10/metabolismo , Esclerose Múltipla Crônica Progressiva/diagnóstico , Adulto , Biomarcadores/análise , Análise Química do Sangue , Avaliação da Deficiência , Progressão da Doença , Feminino , Humanos , Interferon gama/metabolismo , Interleucina-4/metabolismo , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Crônica Progressiva/metabolismo , Prognóstico , Estatística como Assunto , Subpopulações de Linfócitos T/imunologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUND: Rituximab, a monoclonal antibody against the B-cell-specific surface protein CD20, is being evaluated for treatment of multiple sclerosis and neuromyelitis optica. Both diseases are restricted to the brain and cerebrospinal fluid (CSF). Whereas the ability of rituximab to deplete B cells in peripheral blood and tissue is well known, little information is available about the ability of rituximab to penetrate the barriers separating brain and CSF from the serum compartment. OBJECTIVE: To measure rituximab levels in serum and CSF of rituximab-treated patients and correlate them with CSF and response markers. METHODS: Fourteen paired serum/CSF samples of patients with autoimmune nervous system disorder were analyzed for up to 43 weeks after rituximab application. RESULTS: Rituximab remains detectable within the CSF after i.v. application for up to 24 weeks. Furthermore, levels of rituximab in CSF correlate significantly with the integrity of the blood CSF barrier.
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Anticorpos Monoclonais/farmacocinética , Barreira Hematoencefálica , Fatores Imunológicos/farmacocinética , Esclerose Múltipla/tratamento farmacológico , Neuromielite Óptica/tratamento farmacológico , Idoso , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/líquido cefalorraquidiano , Anticorpos Monoclonais Murinos , Linfócitos B/citologia , Linfócitos B/efeitos dos fármacos , Feminino , Citometria de Fluxo , Humanos , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/líquido cefalorraquidiano , Injeções Intravenosas , Contagem de Linfócitos , Masculino , Esclerose Múltipla/líquido cefalorraquidiano , Esclerose Múltipla/imunologia , Neuromielite Óptica/líquido cefalorraquidiano , Neuromielite Óptica/imunologia , Rituximab , Adulto JovemRESUMO
Cerebrospinal fluid analysis is the method of choice in CNS infection and provides the basis for appropriate treatment. Due to the proximity of CSF and CNS, the infectious agent may be detected directly by microscopy or antigen or nucleic acid detection--the latter by polymerase chain reaction--in native CSF or after culture. Furthermore, intrathecal antibody synthesis against the infectious agent may identify the cause of infection. This indirect antigen detection method requires correction for a systemic antibody response and a blood-CSF barrier disturbance. The following text gives an overview of appropriate detection methods and their relevance to the most important CNS infections.
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Infecções do Sistema Nervoso Central/diagnóstico , Líquido Cefalorraquidiano/microbiologia , Líquido Cefalorraquidiano/virologia , Encefalite/diagnóstico , Meningite/diagnóstico , Complexo AIDS Demência/líquido cefalorraquidiano , Complexo AIDS Demência/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/líquido cefalorraquidiano , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/etiologia , Anticorpos/líquido cefalorraquidiano , Antígenos/líquido cefalorraquidiano , Infecções do Sistema Nervoso Central/líquido cefalorraquidiano , Infecções do Sistema Nervoso Central/etiologia , Encefalite/líquido cefalorraquidiano , Encefalite/etiologia , Meningite/líquido cefalorraquidiano , Meningite/etiologia , Microscopia , Ácidos Nucleicos/líquido cefalorraquidiano , Reação em Cadeia da Polimerase , Sensibilidade e EspecificidadeRESUMO
We report the case of a 22-years old genotypic women suffering from a relapsing-remitting multiple sclerosis (MS) according to the Poser criteria. In this patient, a gender change had been performed by androgen-supplementation and surgical intervention. During gender change, the patient experienced further relapses. Different immunomodulatory and immunosuppressive treatment strategies did not stabilise the course of MS in this patient. Actually, an escalating therapy with mitoxantrone has been initiated. During the observation period the patient received long-term testosterone-supplementation. Testosterone levels were elevated in the serum of this genotypic female MS patient under such a hormonal treatment compared to normal ranges before. The clinical course of the patient is presented in this case. As there are several studies investigating an immunomodulatory impact of hormones on the course of MS or experimental allergic encephalomyelitis, we discuss the presented case and a possible influence of androgens in this patient.
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Androgênios/administração & dosagem , Genitália Feminina/cirurgia , Esclerose Múltipla Crônica Progressiva/fisiopatologia , Esclerose Múltipla Recidivante-Remitente/fisiopatologia , Testosterona/administração & dosagem , Adulto , Progressão da Doença , Feminino , Seguimentos , Humanos , Esclerose Múltipla Crônica Progressiva/cirurgia , Esclerose Múltipla Recidivante-Remitente/cirurgiaRESUMO
Fatigue describes the presence of a pronounced and advanced state of weariness. People with fatigue need more energy and it takes more effort to perform different activities than expected when compared to the patients disability. Fatigue can be observed in up to 92 % of patients suffering from multiple sclerosis. In the presented study, the German fatigue severity scale (dFSS) was established following the English "Fatigue Severity Scale". We enrolled 20 patients suffering from a primary relapsing multiple sclerosis and compared them to 20 healthy controls. Fatigue was detected if at least 4 points were reached in the dFSS. The dFSS demonstrated high validity and reliability. The dFSS is able to differentiate patients with fatigue from healthy controls. As consequence, the dFSS can be used to evaluate fatigue in German speaking individuals. The presented data demonstrated a good internal consistence. The scale is able to measure fatigue in an economic and rapid fashion. Therefore, it can be used in clinical situations for measuring fatigue in German speaking individuals.
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Esclerose Múltipla/diagnóstico , Esclerose Múltipla/fisiopatologia , Fadiga Muscular/fisiologia , Adulto , Análise Fatorial , Feminino , Alemanha , Humanos , Idioma , Masculino , Esclerose Múltipla Crônica Progressiva/fisiopatologia , Reprodutibilidade dos TestesRESUMO
Fatal familial insomnia (FFI) is a hereditary prion disease caused by a mutation in codon 178 of the prion protein gene PRNP on chromosome 20. It is characterized by disturbed night sleep, resulting in daily vigilance perturbations and a variety of other neurological symptoms. We present the case of a 46-year-old woman deteriorating despite immunosuppressive treatment which was initiated suspecting cerebral vasculitis as the cause of her progressive neurological symptoms. The correct diagnosis was established only post mortem. Based on the case presented here, we discuss typical clinical symptoms and imaging findings. In particular, we outline how modern diagnostic methods such as positron emission tomography with [(15)O]H(2)O and [(18)F]FDG and single photon emission computed tomography can add valuable information to results from conventionally performed imaging techniques and genetic testing.
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Fluordesoxiglucose F18 , Imunossupressores/uso terapêutico , Insônia Familiar Fatal/diagnóstico , Insônia Familiar Fatal/tratamento farmacológico , Tomografia por Emissão de Pósitrons/métodos , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Água , Evolução Fatal , Feminino , Humanos , Pessoa de Meia-Idade , Radioisótopos de Oxigênio , Compostos RadiofarmacêuticosRESUMO
BACKGROUND: Interferon-beta (INF-beta) is effective and used in reducing exacerbation frequency and disease progression in multiple sclerosis. In certain circumstances, INF-beta can lead to rare side effects. AIMS OF THE STUDY: We report the case of a 34-year-old female patient satisfying the McDonald criteria of multiple sclerosis without showing typical pathologic changes in cerebrospinal fluid (CSF). After introduction of INF-beta treatment, she quickly developed further progression of her disseminated neurological symptoms and finally an ischemic cerebral infarction. METHODS: Evaluation of the patient included arterial angiography, magnetic resonance and positron emission tomography, histopathological assessment as well as a broad spectrum of serum and CSF analysis. RESULTS: All diagnostic evaluations and the clinical course revealed evidences for a primary angiitis of the CNS. We discuss the possible worsening due to inappropriate INF-beta treatment in cerebral angiitis promoting severe cerebrovascular insufficiency. CONCLUSION: The authors suggest that all diagnostic multiple sclerosis criteria including typical CSF findings should be ascertained before INF-beta treatment is initiated.
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Interferon beta/efeitos adversos , Esclerose Múltipla Recidivante-Remitente/diagnóstico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Acidente Vascular Cerebral/induzido quimicamente , Vasculite do Sistema Nervoso Central/complicações , Vasculite do Sistema Nervoso Central/diagnóstico , Adjuvantes Imunológicos/efeitos adversos , Adulto , Encéfalo/irrigação sanguínea , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Angiografia Cerebral , Artérias Cerebrais/diagnóstico por imagem , Artérias Cerebrais/efeitos dos fármacos , Artérias Cerebrais/patologia , Circulação Cerebrovascular/efeitos dos fármacos , Erros de Diagnóstico , Progressão da Doença , Feminino , Humanos , Doença Iatrogênica/prevenção & controle , Imageamento por Ressonância Magnética , Esclerose Múltipla Recidivante-Remitente/líquido cefalorraquidiano , Fibras Nervosas Mielinizadas/patologia , Tomografia por Emissão de Pósitrons , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/fisiopatologia , Vasculite do Sistema Nervoso Central/fisiopatologiaRESUMO
Intravenous immunoglobulins (IVIG) have been effective in reducing multiple sclerosis (MS) disease activity and improving disability scores. However, the mechanism by which this beneficial effect is achieved remains unclear. An effect of IVIG on pro- and anti-inflammatory cytokines which are thought to play a role in the disease process - has been postulated in a number of animal and ex vivo studies. Hence, we performed a study on 34 patients with secondary progressive (SP) MS being treated with monthly IVIG or placebo for two years according to the protocol of the ESIMS study. Clinical outcome measures and cytokine production (interferon gamma, tumour necrosis factor alpha, interleukin-4 and -10) were recorded in all patients and compared with respect to the treatment group. Against our expectations, IVIG did not reduce the relapse rate or the progression of disability or cytokine production. Our data argue against an enduring immunomodulating effect of IVIG, at least in SPMS.
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Citocinas/sangue , Imunoglobulinas Intravenosas/uso terapêutico , Linfócitos/imunologia , Esclerose Múltipla Crônica Progressiva/tratamento farmacológico , Esclerose Múltipla Crônica Progressiva/imunologia , Adulto , Feminino , Humanos , Fatores Imunológicos/uso terapêutico , Linfócitos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Crônica Progressiva/sangue , RecidivaRESUMO
HISTORY AND ADMISSION FINDINGS: A 37-year-old woman was admitted with total loss of vision of the left eye within 24 hours. Additionally, she complained about fatigue, headache, chills, fever, muscle pain and neck stiffness since 4 days. At admission, the body temperature was 38.7 degrees C. Neurological examination revealed papilledema and meningism. INVESTIGATIONS: Ophthalmologic findings were consistent with a papillitis. The vision was lost, the pattern-shift checkerboard visual evoked potentials were not measurable. MRI of the brain and the optical nerve was without pathological findings, meningeal or cerebral Gadolinium enhancement was not present. The CSF analysis yielded a lymphocytic meningitis with 249 cells/mm (3), the glucose ratio of cerebrospinal fluid and serum was normal. DIAGNOSIS, TREATMENT AND COURSE: The papillitis was treated unsuccessfully with high-dose methylprednisolone, the left eye remained blind. Persistence of the pleocytosis under initial treatment with aciclovir and ceftriaxone, reduction of the glucose ratio of cerebrospinal fluid and serum and intrathecal immunoglobuline A -- synthesis required a change of the diagnostic and therapeutic regimen. Various common and rare differential diagnoses were considered and ruled out, a chronic meningitis of unclear aetiology with the complication of amaurosis was diagnosed. In consideration of the most probable diagnosis, a tuberculostatic therapy was initiated. A prolonged reduction of the pleocytosis and normalization of cerebrospinal fluid parameters could be observed. CONCLUSIONS: A large number of aetiologies can cause chronic meningitis; this case report reviews the most important differential diagnoses and highlights the limitations of the diagnostic work-up although various methods are available. Clinical course and symptoms of chronic meningitis are mild to moderate and may even be absent, but it can cause severe complications.
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Cegueira/etiologia , Potenciais Evocados Visuais/fisiologia , Meningite/complicações , Meningite/diagnóstico , Meningite/fisiopatologia , Adulto , Encéfalo/patologia , Doença Crônica , Feminino , Humanos , Linfócitos/patologia , Imageamento por Ressonância Magnética , Reconhecimento Visual de ModelosRESUMO
OBJECTIVES: A number of neurological syndromes may be evoked by involvement of the nervous system due to systemic diseases such as lupus erythematodes, sarcoidosis, Behçet's disease and Sjögren's syndrome (SS) and may be confounded with another chronic inflammatory disease which is restricted to the central nervous system, e.g. multiple sclerosis (MS). Because of different treatment strategies, it is important to distinguish between these different autoimmune diseases. RESULTS: Neither clinical signs nor additional analyses such as serological findings or cerebrospinal fluid (CSF) analysis are able to differentiate between the diseases with certainty. Nevertheless, taking all findings together, diagnosis may be possible. CONCLUSION: Here we compare typical clinical and CSF findings in MS, neurosarcoidosis, neurolupus, neuro-Behçet and nervous system involving SS with special emphasis on those findings allowing differentiation of the respective diseases by reviewing the literature.
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Doenças Autoimunes do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso Central/diagnóstico , Doenças Autoimunes do Sistema Nervoso/líquido cefalorraquidiano , Doenças Autoimunes do Sistema Nervoso/imunologia , Biomarcadores , Doenças do Sistema Nervoso Central/líquido cefalorraquidiano , Doenças do Sistema Nervoso Central/imunologia , Doença Crônica , Diagnóstico Diferencial , HumanosRESUMO
Glatiramer acetate (GLAT) is a well tolerated and safe immunomodulatory drug for the treatment of relapsing-remitting multiple sclerosis. The most commonly recognized side effects are localized injection site reactions consisting of pain, pruritus, mild erythema and induration, which sometimes persist for several days. We describe the first case of a biopsy-proven lymphocytic infiltration (T-cell pseudolymphoma) with the clinical appearance of a figured erythema on the ventrolateral thighs in the first four weeks under GLAT treatment, resolving without any evidence of recurrence despite ongoing therapy. A T-cell pseudolymphoma is a very rare side effect of GLAT treatment. For clinical purposes it is important to state that re-exposition after GLAT-induced pseudolymphoma is possible without permanent sequelae.
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Imunossupressores/efeitos adversos , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Peptídeos/efeitos adversos , Pseudolinfoma/induzido quimicamente , Dermatopatias/induzido quimicamente , Adulto , Acetato de Glatiramer , Humanos , Hiperpigmentação/induzido quimicamente , Hiperpigmentação/imunologia , Linfócitos/imunologia , Masculino , Esclerose Múltipla Recidivante-Remitente/imunologia , Pseudolinfoma/imunologia , Dermatopatias/imunologiaRESUMO
A number of neurological syndromes may be evoked by involvement of the nervous system due to systemic diseases such as lupus erythematosus, sarcoidosis, Behcet's disease, and Sjogren's syndrome. Because of different treatment strategies, it is important to distinguish between these different diseases. Neither clinical signs nor additional analyses such as serological findings or cerebrospinal fluid analysis are able to differentiate between the diseases with certainty. Nevertheless, diagnosis may finally be made taking all findings together. Here we compare typical clinical and cerebrospinal fluid findings in neurosarcoidosis, neurolupus, neuro-Behcet, and nervous system involving Sjogren's syndrome, with special emphasis on those findings allowing differentiation of the respective diseases.
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Doenças do Sistema Nervoso Central/líquido cefalorraquidiano , Doenças do Sistema Nervoso Central/diagnóstico , Inflamação/líquido cefalorraquidiano , Inflamação/diagnóstico , Síndrome de Behçet/líquido cefalorraquidiano , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/imunologia , Doenças do Sistema Nervoso Central/imunologia , Doença Crônica , Guias como Assunto , Humanos , Inflamação/imunologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/líquido cefalorraquidiano , Vasculite Associada ao Lúpus do Sistema Nervoso Central/diagnóstico , Vasculite Associada ao Lúpus do Sistema Nervoso Central/imunologia , Padrões de Prática Médica , Sarcoidose/líquido cefalorraquidiano , Sarcoidose/diagnóstico , Sarcoidose/imunologia , Síndrome de Sjogren/líquido cefalorraquidiano , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/imunologia , SíndromeRESUMO
Multiple sclerosis (MS), a disease of presumably autoimmune aetiology, is characterized by inflammation, demyelination and axonal degeneration in the central nervous system. Current treatment concepts target the inflammatory activity, reducing the number of relapses and inflammatory lesions on magnetic resonance imaging as well as the proinflammatory cytokine production in blood lymphocytes. Recently, the neuroprotective aspect of inflammation has been documented and is thought to be mediated by neurotrophins, like brain-derived neurotrophic factor (BDNF). The question whether the in vitro BDNF production in MS patients and healthy controls is influenced by the immunomodulatory agents interferon beta (IFN-beta) and immunoglobulin G (Ig) is addressed. A significantly increased BDNF production in MS patients was found compared with normal controls (mean +/- SD: 492 +/- 172 pg/mL versus 217 +/- 55 pg/mL, P < 0.001). IFN-beta and low-dose Ig had no effect on BDNF production, whereas high-dose Ig reduced in vitro BDNF production in MS patients significantly (to 409 +/- 125 pg/mL, P = 0.001). These in vitro findings might indicate that Igs in high doses potentially interfere with neuroprotective mechanisms despite their potent anti-inflammatory properties.
Assuntos
Adjuvantes Imunológicos/farmacologia , Fator Neurotrófico Derivado do Encéfalo/biossíntese , Interferon beta/farmacologia , Linfócitos/metabolismo , Esclerose Múltipla Recidivante-Remitente/imunologia , Adulto , Fator Neurotrófico Derivado do Encéfalo/imunologia , Feminino , Humanos , Imunoglobulina G/farmacologia , Técnicas In Vitro , Interferon gama/metabolismo , Linfócitos/efeitos dos fármacos , Linfócitos/imunologia , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Neuroimunomodulação/imunologiaRESUMO
OBJECTIVES: The mechanism by which intravenous immunoglobulins (immunoglobulin G, IgG) exert their beneficial effect on multiple sclerosis (MS) is unknown. Furthermore, there is uncertainty about the optimal dosage of IgG. Therefore, we investigated the influence of different IgG dosages on cytokine production in MS. MATERIALS AND METHODS: Twenty-five MS patients and 15 healthy controls were enrolled. We measured the production of interferon gamma (IFN-gamma), tumour necrosis factor alpha (TNF) and interleukin 10 (IL-10) in peripheral blood lymphocytes by flowcytometry after stimulation without and with IgG in different doses (1, 5 and 10 mg/ml). RESULTS: IFN-gamma and TNF were decreased significantly (P = 0.001) in the untreated and interferon beta (IFN-beta) treated patients after stimulation with IgG. In contrast, IL-10 production was significantly enhanced (P = 0.001) at least in the untreated patient group. The reduction of the pro-inflammatory cytokines IFN-gamma and TNF after stimulation with different IgG doses was clearly dose-dependent in all groups. CONCLUSION: Besides a suppression of the pro-inflammatory cytokines IFN-gamma and TNF, IgG enhances the anti-inflammatory cytokine IL-10. This effect is dose-dependent, speaking in favour of higher IgG doses in the treatment of MS.