Detection Of Antineuronal Antibodies Research Articles

Paraneoplastic cerebellar degeneration

Introduction. Paraneoplastic cerebellar degeneration (PCD) is an immune-mediated and rapidly progressive cerebellar syndrome that develops as a result of a cross-immune response to the common antigens for the tumor and cerebellar cells. Timely diagnosis and treatment of PCD improves the functional status and survival of these patients.Objective. To analyze the clinical, laboratory and neuroimaging characteristics of PCD case series in comparison with literature data.Material and methods. 16 patients with PCD (13 women, 3 men) were examined. An assessment of the clinical presentation, brain MRI study, blood and cerebrospinal fl uid laboratory tests were carried out, the data of cancer search and patients follow-up were analyzed.Results. The median age of PCD patients was 55 years, the duration of the disease was 8.5 months (range 4 to 16 months). In 12 patients, PCD was the fi rst manifestation of cancer. The clinical prentation was presented by rapidly progressive cerebellar ataxia, often in combination with oculomotor disturbances, pyramidal and bulbar syndrome, hand tremor and dystonia. An associated cancers were detected in 13 patients (81%). Antineuronal antibodies were found in 14 patients (88%): anti-Yo-1, antibodies to amphiphysin, anti-Hu, anti-CV2 and anti-GAD. Mild atrophic changes of the cerebellum were found in 6 patients, and in 2 cases cerebellar hemiatrophy was observed.Conclusion. PCD is a rare disabling but potentially curable disease. The basis of diagnosis is the analysis of the clinical presentation and neuroimaging data, the detection of antineuronal antibodies and in fl ammatory changes in the cerebrospinal fl uid, as well as a thorough cancer search.

Autoimmune Mechanisms in Focal Epilepsy of Unknown Cause

ABSTRACT The manifestation of immunological findings in diverse disorders presenting with seizures points to autoimmunity and inflammation in the etiology of epilepsy. Typical examples of autoimmunity-associated epilepsy are autoimmune encephalitis, Rasmussen encephalitis, and glutamic acid decarboxylase (GAD) antibody-positive temporal lobe epilepsy (TLE). The last entity is a typical example of antibody-positive focal epilepsy of unknown cause (FEUC). One of the most prominent findings emphasizing the coexistence of epilepsy and autoimmunity is the detection of anti-neuronal antibodies in patients manifesting with seizures. Emergence of antibody-producing plasma cells in the early course of GAD-antibody-positive TLE and induction of seizures in rodents upon intracerebral administration of N-methyl-D-aspartate receptor antibodies indicate that anti-neuronal antibodies may play a causal (rather than bystander) role in the induction of seizures. By contrast, innate immunity of the central nervous system (CNS) and infiltrating cytotoxic T-cells appear to participate in Rasmussen encephalitis and autoimmune encephalitis with antibodies to intracellular antigens. In addition, repetitive seizures may activate glial cells through the release of damage-associate molecular pattern mediators and activation of toll-like receptors, which in turn leads to disrupted blood–brain barrier and increased cerebral infiltration of peripheral blood immune cells. In conclusion, complex interactions of humoral and cellular immunity in the CNS appear to cause or at least contribute to seizure induction in FEUC. The nature of these interactions has recently started to be understood. Investigation of these mechanisms is substantial for the discovery of new treatment strategies and biomarkers in epilepsy.

Autoantibody-Mediated Encephalitis.

Acute and subacute disturbances of wakefulness and cognitive function are common neurological manifestations in the hospital and in outpatient care. An important element of the differential diagnosis was described only a few years ago: autoimmune encephalitis, a condition whose diagnosis and treatment pose an interdisciplinary challenge. This review is based on pertinent publications from the years 2005-2017 that were retrieved by a selective search in PubMed, and on the authors' personal experience and case reports. The incidence of autoimmune encephalitis in Germany is estimated at 8-15 cases per million persons per year. In some patients with psychotic manifestations or impaired consciousness of acute or subacute onset, an autoimmune patho - genesis can be demonstrated by the laboratory detection of autoantibodies against neuronal target antigens (e.g., glutamate receptors). Testing of this type should be performed in patients with inflammatory changes in the cerebrospinal fluid or on magnetic resonance imaging (MRI), or those who have had an otherwise unexplained first epileptic seizure or status epilepticus. The cumulative sensitivity of testing for all potentially causative antineuronal antibodies in patients with clinically defined autoimmune encephalitis is estimated at 60-80 %. Figures on cumulative specificity are currently unavailable. The detection of antineuronal antibodies in patients with the corresponding appropriate symptoms implies the diagnosis of autoimmune encephalitis. Observational studies have shown that rapidly initiated immunosuppressive treatment improves these patients' outcomes. Further studies are needed to determine the positive predictive value of antineuronal antibody detection and to develop further treatment options under randomized and controlled conditions.

Antibodies to TRIM46 are associated with paraneoplastic neurological syndromes.

Paraneoplastic neurological syndromes (PNS) are often characterized by the presence of antineuronal antibodies in patient serum or cerebrospinal fluid. The detection of antineuronal antibodies has proven to be a useful tool in PNS diagnosis and the search for an underlying tumor. Here, we describe three patients with autoantibodies to several epitopes of the axon initial segment protein tripartite motif 46 (TRIM46). We show that anti‐TRIM46 antibodies are easy to detect in routine immunohistochemistry screening and can be confirmed by western blotting and cell‐based assay. Anti‐TRIM46 antibodies can occur in patients with diverse neurological syndromes and are associated with small‐cell lung carcinoma.

Limbic encephalitis: Clinical spectrum and long-term outcome from a developing country perspective.

Introduction:Limbic encephalitis (LE) is characterized by rapidly progressive short-term memory loss, psychiatric symptoms and seizures. We describe the clinical spectrum, underlying etiology and long-term follow-up of patients with LE from India.Materials and Methods:This prospective study included patients during the period of January 2009 and December 2011 with the clinical features consistent with LE with one or more of the following: (1) Magnetic resonance imaging (MRI) evidence of temporal lobe involvement; (2) cerebrospinal fluid inflammatory abnormalities, or (3) detection of antineuronal antibodies. Patients with metastasis, infection, metabolic and nutritional deficits, stroke, were excluded.Results:There were 16 patients (9 females), mean age of presentation was 36.6 years (range 15-69 years). The mean duration of symptoms before presentation was 11 months (range 5 days-2 years). The most common symptom at presentation was short-term memory impairment in 7 patients followed by seizures in 5 and behavioral changes in three. Nine patients had seizures, 11 had change in behavior, language involvement in eight, cerebellar features in 3 and autonomic dysfunction in two. Four patients had associated malignancy, 3 of four presented with neurological symptoms and on investigations found to be have malignancy. Antineuronal antibody testing was done in 6 of 12 non paraneoplastic and two paraneoplastic patients, one positive for N-methyl-D-aspartate and one for anti-Hu antibody. MRI brain showed typical fluid attenuated inversion recovery or T2 bilateral temporal lobe hyperintensities in 50% of patients. At a mean follow-up of 21 months (3-36 months), 10 patients improved, 4 patients remained same and two patients expired.Conclusion:Early recognition of LE is important based upon clinical, MRI data in the absence of antineuronal surface antibody screen in developing nations. Early institution of immunotherapy will help in improvement in outcome of these patients in long-term.

Diagnostic Accuracy of Different Immunological Methods for the Detection of Antineuronal Antibodies in Paraneoplastic Neurological Syndromes

The aim of this work was to evaluate the diagnostic accuracy of three different analytical methods for the detection of antineuronal antibodies and outline how they might be used to diagnose Paraneoplastic Neurological Syndromes (PNS) in a more effectively and rationally way. One hundred and four patients with neurological diseases were studied: 38 with paraneoplastic neurological disorder, 44 with other neurological diseases, and 22 with systemic autoimmune diseases and neurological disorders. 20 healthy subjects and 18 subjects with tumour without neurological disorders were also studied. Antineuronal antibodies were tested using three methods: Western blot (WB); Line-blot (LB); and indirect immunofluorescence (IIF) on primate cerebellum. The diagnostic sensitivity of the IIF, WB and LB methods was 28.9%, 26.3% and 36.8%, respectively, and their specificity was 95.2%, 97.1% and 98.1% respectively. The combined use of the three methods brought the sensitivity to 39.4%. The results of this study show that the methods used in clinical laboratories for the detection of antineuronal antibodies have good specificity. Among the three methods assessed, LB showed the highest diagnostic accuracy and also allowed for recognition of fine antibody specificities. According to these results we can suggest that LB should be used as the method of choice to search for paraneoplastic antibodies.

Síndrome cerebeloso paraneoplásico como primera manifestación de un cáncer de ovario

We describe the case of a woman with an ovarian tumor in whom the first manifestation was subacute cerebellar degeneration, a paraneoplastic syndrome characterized by bilateral, symmetric cerebellar dysfunction, which usually manifests as ataxia of the trunk and extremities with subsequent dysarthria. The development of acute or subacute cerebellar manifestations in a female patient without cerebral tumor or known metastasis should lead to investigation of an unknown tumor. Elevated tumoral markers, as well as detection of antineuronal antibodies in a patient with cerebellar dysfunction is, by itself, sufficient to warrant surgery, even when diagnostic imaging tests are negative.

Autoimmunity in paraneoplastic neurological syndromes.

In patients with Paraneoplastic Neurological Disorders, the researcher detected several autoantibodies reacting with neuronal antigens and tumors; their characteristics supported the hypothesis that autoimmunity plays a part in these diseases and gave impetus to the study of these neurological disorders. The relationship between detection of anti-neuronal antibodies, clinical syndromes, and certain types of tumors suggested the utility of these antibodies as a new tool for clinical diagnosis, although their function in the pathogenesis of the various syndromes is still unclear. This paper intends to review the characteristics of the anti-neuronal antibodies so far identified, their correlation with clinical syndromes, and the function of antigens. In addition, the paper will offer some insights on the immunological mechanisms of neuronal damage and on treatment options.

Detection of anti-neuronal antibodies in adolescents with anorexia nervosa

Detection of anti-neuronal antibodies in adolescents with anorexia nervosa

An antineuronal antibody cross-reacting with erythrocytes and lymphocytes in systemic lupus erythematosus

An antibody with erythrocyte and lymphocyte activity, present in the sera of patients with systemic lupus erythematosus (SLE), demonstrated additional reactivity with neurons. The neuronal reactivity was greater with cortical neurons than with cerebellar and caudate nucleus neurons, was predominantly IgG, and was immunologically specific. Selected sera from 22 patients with active SLE were tested for the presence of antineuronal antibody. Eleven of 12 sera obtained from patients with neuropsychiatric disease demonstrated definite neuron reactivity, in contrast to only 2 of 10 sera obtained from patients without evidence of neuropsychiatric involvement (P less than 0.005). Five of 21 sera from patients with rheumatoid arthritis, but no sera from 5 other disease control groups, contained antineuronal antibody. Serial studies of 2 SLE patients with transient psychotic episodes demonstrated a close association between antibody titer and the appearance of psychosis in one. These observations suggest that the detection of antineuronal antibodies in patients with SLE may be of value in the diagnosis and management of neuropsychiatric complications.