Paraneoplastic Neurologic Syndromes - An Update on Current Understanding and Future Perspectives (original) (raw)
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Immunological Features of Paraneoplastic Neurological Syndromes
International Journal of Immunopathology and Pharmacology, 2004
Paraneoplastic neurological syndromes are a rare group of disorders that occur in 1 – 2 % of people with malignancy. They are usually caused by an immune response, triggered by and directed against a tumour, that cross-reacts with protein expressed by the peripheral or central nervous system. Any part of the nervous system can be affected and patients often develop severe and permanent disability. Diagnosis can be difficult as in two-thirds of patients the neurological problems appear up to 5 years before the tumour manifests. However, certain of these syndromes are often associated with specific serum autoantibodies that can be useful both in diagnosis of the neurological syndrome and in focusing the search for a particular tumour. Thus, these antibodies can allow earlier identification and treatment of cancer and, potentially, a reduction in morbidity and mortality. It was only in the 1980s that the first onconeural autoantibodies were characterized and their associations with cli...
Paraneoplastic neurological syndromes: a practical approach to diagnosis and management
Practical Neurology, 2021
Paraneoplastic neurological syndromes (PNS) are the immune-mediated effects of a remote cancer and are characterised by an autoantibody response against antigens expressed by the tumour. Classically, well-characterised ‘onconeuronal’ antibodies target intracellular antigens and hence cannot access their antigens across intact cell membranes. The pathogenic mediators are likely to be neuronal-specific T cells. There is a variable response to immunotherapies and the clinical syndrome helps to direct the search for a specific set of tumours. By contrast, many newly emerging autoantibodies with oncological associations target cell surface epitopes and can exert direct pathogenic effects on both the central and peripheral nervous systems. Patients with these cell-surface directed autoantibodies often clearly respond to immunotherapies. Overall, the clinical, serological and oncological features in an individual patient help to determine the clinical relevance of the syndrome and hence gu...
Journal of Biosciences
Paraneoplastic neurological syndromes (PNS) are a group of rare and severe immune-mediated disorders that affect the nervous system in patients with cancer. The best way to diagnose a paraneoplastic neurological disorder is to identify anti-onconeural protein antibodies that are specifically associated with various cancers. The aim of this multicentric study was to clinically and immunologically characterize patients with PNS and study their association with cancer. Patients suspected to have PNS were enrolled from various clinical centres and were characterized immunologically. This study population consisted of 112 patients. Onset of PNS was mainly subacute (76%). PNS patients had various neurological disorders and symptoms. PNS developed before the diagnosis of cancer in 28 definite PNS patients and in six suspected PNS patients. The most frequent autoantibodies detected in PNS patients were anti-Hu and anti-Yo. One definite PNS patient with cerebellar syndrome had anti-Tr antibody and seven patients had atypical antibodies. The literature associates these antibodies with various neurological disorders and cancers. Our observations confirm the important role of autoantibodies in PNS and their importance for the early diagnosis of cancer in PNS patients.
Journal of Neurology, Neurosurgery & Psychiatry, 2008
Objective Anti-Hu antibodies (Hu-Ab) and anti-CV2/CRMP5 antibodies (CV2/CRMP5-Ab) have been identified in association with paraneoplastic neurological disorders. However, it is not clear whether these antibodies are associated with specific neurological symptoms or are only markers of anti-cancer immune reaction. Methods To address this question, we compared 37 patients with CV2/CRMP5-Ab and 324 patients with Hu-Ab. Results Whereas the age and sex ratio were the same between the two groups, the distribution of neurological symptoms was not. Patients with CV2/CRMP5-Ab presented more frequently cerebellar ataxia, chorea, uveo/retinal symptoms and myasthenic syndrome (Lambert-Eaton myasthenic syndrome LEMS or myasthenia gravis). They also had better Rankin score. On the opposite, dysautonomia, brainstem encephalitis and peripheral neuropathy were more frequent in patients with Hu-Ab. Limbic encephalitis occurred similarly in both groups. Small cell lung cancer (SCLC) was the most frequently associated tumor in both groups of patients while malignant thymoma was observed only in patients with CV2/CRMP5-Ab. In particular, patients with CV2/CRMP5-Ab and thymoma developed more frequently myasthenic syndrome while patients with SCLC developed more frequently neuropathies. Chorea and myasthenic syndrome were only seen in patients with CV2/CRMP5-Ab. The median survival time was significantly longer in patients with CV2/CRMP5-Ab and this effect was not dependent on the type of tumor. Interpretation Our data demonstrate that in patients with paraneoplastic neurological syndromes, the neurological symptoms and survival vary with both the type of associated onco-neural antibody and the type of tumor.
Paraneoplastic neurological syndromes
Orphanet Journal of Rare Diseases, 2007
Paraneoplastic neurological syndromes (PNS) can be defined as remote effects of cancer that are not caused by the tumor and its metastasis, or by infection, ischemia or metabolic disruptions. PNS are rare, affecting less than 1/10,000 patients with cancer. Only the Lambert-Eaton myasthenic syndrome is relatively frequent, occurring in about 1% of patients with small cell lung cancer. PNS can affect any part of the central and peripheral nervous system, the neuromuscular junction, and muscle. They can be isolated or occur in association. In most patients, the neurological disorder develops before the cancer becomes clinically overt and the patient is referred to the neurologist who has the charge of identifying a neurological disorder as paraneoplastic. PNS are usually severely disabling. The most common PNS are Lambert-Eaton myasthenic syndrome (LEMS), subacute cerebellar ataxia, limbic encephalitis (LE), opsoclonus-myoclonus (OM), retinopathies (cancerassociated retinopathy (CAR) and melanoma-associated retinopathy (MAR), Stiff-Person syndrome (SPS), chronic gastrointestinal pseudoobstruction (CGP), sensory neuronopathy (SSN), encephalomyelitis (EM) and dermatomyositis. PNS are caused by autoimmune processes triggered by the cancer and directed against antigens common to both the cancer and the nervous system, designated as onconeural antigens. Due to their high specificity (> 90%), the best way to diagnose a neurological disorder as paraneoplastic is to identify one of the well-characterized antionconeural protein antibodies in the patient's serum. In addition, as these antibodies are associated with a restricted range of cancers, they can guide the search for the underlying tumor at a stage when it is frequently not clinically overt. This is a critical point as, to date, the best way to stabilize PNS is to treat the cancer as soon as possible. Unfortunately, about one-third of patients do not have detectable antibodies and 5% to 10% have an atypical antibody that is not well-characterized. As PNS are believed to be immune-mediated, suppression of the immune response represents another treatment approach.
Paraneoplastic Syndromes Affecting the Nervous System
Seminars in Oncology, 2006
Paraneoplastic syndromes can affect virtually any portion of the nervous system. Most paraneoplastic syndromes are believed to be caused by an autoimmune reaction to an "onconeural" antigen shared by the cancer and the nervous system. The immune reaction may retard growth of the cancer, but it also damages the nervous system. Specific autoantibodies found in some individual paraneoplastic syndromes are usually associated with specific tumors. Neurological disorders, clinically and pathologically identical to paraneoplastic syndromes, may occur in some patients without cancer, but paraneoplastic antibodies are not found in these patients. The diagnosis of a paraneoplastic syndrome is based on its increased incidence in patients with cancer, the occasional response of the neurological syndrome to treatment of the underlying cancer, or the presence of specific autoantibodies. Some paraneoplastic syndromes respond to treatment of the underlying cancer or to immunosuppression but, for most syndromes, no effective treatment exists.
Paraneoplastic neurologic syndrome: A practical approach
Annals of Indian Academy of Neurology, 2012
The first description of PNS was in the 19 th century by a French physician M Auche` who described the peripheral nervous system involvement in cancer patients in 1890. [3] The first antibody described was PCA-1 (Purkinje Cell Antibody 1), by Greenlee and Brashear in 1983, in two patients with ovarian carcinoma and paraneoplastic cerebellar degeneration. [4] More syndromes and antibodies have been subsequently described and the list of the syndromes and antibodies continue to increase day by day. Pathophysiology PNS are mainly autoimmune. [1] When the body tries to eliminate tumor cells, it launches an immune response, and this response can target normal neural tissues. [5] This could be mediated by antibodies or by T-cells. Thus, most of the PNS reflect a nervous system-specific autoimmune attack initiated by onconeural antigens released to the peripheral lymphoid tissue from an unsuspected primary or recurrent neoplasm. [2] Frequently, a cerebrospinal fluid (CSF) study in these patients reveals lymphocytic pleocytosis, elevated protein, increased IgG synthesis and oligoclonal bands, supporting the immunological pathology. In a recent European study, abnormal CSF was
Paraneoplastic Neurologic Syndrome in the PNS Euronetwork Database
Archives of Neurology, 2010
Background: Paraneoplastic neurologic syndrome (PNS) represents the remote effects of cancer on the nervous system. Diagnostic criteria for the syndrome were published by the PNS Euronetwork and form the basis of a database to collect standardized clinical data from patients with PNS. Objectives: To analyze various types of PNS, frequent tumor and antibody associations, clinical characteristics of individual syndromes, and possible therapeutic and prognostic strategies.
What a Clinician Must Know Regarding Diagnosis of Paraneoplastic Neurological Syndromes
2012
About 3–5 % of patients with small-cell lung cancer and 15– 20 % of patients with thymoma develop paraneoplastic neurological syndromes (PNS). Less than 1 % of patients with other types of tumours develop paraneoplastic neurological symptoms [1]. As PNS are also associated with some benign tumours, eg, teratoma and thymoma, malignant properties are not a necessary component of the tumour, but expression of a relevant protein is necessary for the development of a PNS. Tumours in patients with PNS express proteins that are normally only expressed in the nervous system. The tumour protein is identical to the neuronal protein, but is identified as foreign or non-self by the immune system when expressed by the tumour cell. The body produces antibodies and activates T-cells to these proteins as part of the anti-tumour immune response. The antibodies and T-cells cross the blood-brain or blood-nerve barriers and cross-react with proteins in the nervous system. This cross-reaction leads to l...